Nanostructures for Cancer Therapy

Nanostructures for Cancer Therapy

Nanostructures in Therapeutic Medicine Series

Edited by

Anton Ficai

University Politehnica of Bucharest, Bucharest, Romania

Alexandru Mihai Grumezescu

University Politehnica of Bucharest, Bucharest, Romania

Table of Contents

Cover

Title page

Copyright

List of Contributors

Foreword of the Series

Preface

Chapter 1: Nanotechnology for personalized medicine: cancer research, diagnosis, and therapy

Abstract

1. Introduction

2. Main Types of Cancer

3. Personalized Treatment of Cancer

4. Nanotreatment of Cancer

5. Nanodrugs and Nanocarriers

6. Conclusions

Acknowledgments

Chapter 2: Bioengineered nanomaterials for chemotherapy

Abstract

1. Introduction

2. Polymeric Nanoparticles

3. Carbon Nanotubes

4. Gold Nanoparticles

5. Supermagnetic Iron Oxide Nanoparticles

6. Fullerenes

7. Dendrimers

8. Quantum Dots

9. Conclusions

Acknowledgments

Chapter 3: Biofunctionalized nanomaterials for targeting cancer cells

Abstract

1. Introduction

2. Targeting Strategies for Cancer Cells

3. Combination of Nanostructures With Chemotherapeutic Agents

4. Conclusions

Acknowledgment

Chapter 4: Improving chemotherapy drug delivery by nanoprecision tools

Abstract

1. Introduction

2. Conventional Cancer Treatment

3. Nanoparticles for Chemotherapy Delivery System

4. Challenges Facing Nanomedicine in Oncology

5. Conclusions

Chapter 5: RIPL peptide as a novel cell-penetrating and homing peptide: design, characterization, and application to liposomal nanocarriers for hepsin-specific intracellular drug delivery

Abstract

1. Introduction

2. Cell-Penetrating and Homing Peptide

3. RIPL Peptide for Hpn-Specificity

4. RIPL-Conjugated Liposomes

5. Cytotoxicities of RIPL and RIPL-Lipo

6. Summary

Acknowledgments

Chapter 6: Progress of nanoparticles research in cancer therapy and diagnosis

Abstract

1. Introduction

2. Nanoparticles as Efficient Drug-Delivery Systems

3. Nanoparticles for Cancer Therapy

4. Conclusions

Acknowledgement

Chapter 7: Interfacial engineering of nanoparticles for cancer therapeutics

Abstract

1. Introduction

2. Characteristics of Drug Delivery Carriers

3. Different Types of Nanoparticle-Based Delivery Systems

4. Site-Specific Targeting of Nanoparticles

5. Pharmacokinetics and Biodistribution of Nanoparticles

6. Future Perspectives

Chapter 8: Nanotechnological approaches toward cancer chemotherapy

Abstract

1. Nanotherapeutics

2. The Development of Nanotherapeutics

3. Nanostructures for Cancer Therapy

4. Methods for Fabrication of Nanoparticles

5. Mode of Entry of Nanoparticles in Cells

6. Controlled Drug Delivery Systems

7. Nanoparticles for Cancer Drug Delivery: Active versus Passive Targeting

8. Targeted Drug Delivery Systems

9. Pharmacokinetics of Nanotherapeutics

10. Toxicology of Nanoformulations

11. The Gap Between Laboratory Synthesis and Commercial Viability of Production of Nanoformulations

12. Conclusions

Chapter 9: Cancer therapies: applications, nanomedicines and nanotoxicology

Abstract

1. Introduction

2. Applications of Chemotherapy

3. Nanomedicines for Cancer Therapy

4. Nanotoxicology

5. Conclusions

Acknowledgments

Chapter 10: Multifunctional polymeric micelles as therapeutic nanostructures: targeting, imaging, and triggered release

Abstract

1. Introduction

2. Encapsulation of Drug

3. Drug Delivery

4. Triggered Release

5. Appropriate Targeting

6. Imaging

7. Multifunctional Micelles

8. Conclusions

Chapter 11: Recent advances in diagnosis and therapy of skin cancers through nanotechnological approaches

Abstract

1. Introduction

2. Epidemiology of Skin Cancers

3. Modern Diagnosis of Skin Cancers

4. Modern Treatment of Skin Cancers

5. Nanosystems in the Diagnosis of Skin Cancers

6. Nanosystems in the Therapy of Skin Cancers

7. Conclusions and Perspectives

Chapter 12: Design of nanoparticle structures for cancer immunotherapy

Abstract

1. Introduction

2. Dendritic Cells

3. Targeting Dendritic Cells in Vaccine Development by Nanoparticles

4. Nanoparticle-Based Immunotherapy for Cancer

5. Immunological Properties of Engineered Nanoparticles

6. Conclusions

Chapter 13: Recent advances of folate-targeted anticancer therapies and diagnostics: current status and future prospectives

Abstract

1. Introduction

2. Principles of Folate-Targeting Strategy

3. Folate-Targeted Anticancer Therapy

4. Folate-Targeted Systems as Diagnostic Tools in Cancer

5. Conclusions and Future Prospectives

Acknowledgments

Chapter 14: Anticancer efficiency of curcumin-loaded invertible polymer micellar nanoassemblies

Abstract

1. Introduction

2. Synthesis of Amphiphilic Invertible Polymers

3. Micellization, Self-Assembly, and Invertible Properties of AIPs

4. Self-Assembly of AIPs in Water: Potential for Stimuli-Responsive Drug Delivery

5. Invertible Polymer Micellar Nanoassemblies as a Unique Delivery System Targeted to Osteosarcoma Cells

6. Conclusions

Chapter 15: Dose enhancement effect in radiotherapy: adding gold nanoparticles to tumor in cancer treatment

Abstract

1. Introduction

2. Application of Gold Nanoparticles in Radiotherapy

3. Dose Enhancement due to Gold Nanoparticle Addition

4. Gold Nanoparticle-Enhanced Radiotherapy

5. Conclusions

Acknowledgment

Chapter 16: Silver-based nanostructures for cancer therapy

Abstract

1. Introduction

2. Silver-Based Nanostructures for Tumor Diagnosis

3. Silver-Based Nanostructures for Tumor Targeted and Controlled Delivery Systems

4. Silver-Based Nanostructures for Tumor External-Activated Treatment

5. Conclusions

Acknowledgments

Chapter 17: Ligand-decorated polysaccharide nanocarriers for targeting therapeutics to hepatocytes

Abstract

1. Introduction

2. Different Ligand-Polysaccharide Nanocarriers

3. Conclusions

Chapter 18: Targeted delivery of anticancer drugs: new trends in lipid nanocarriers

Abstract

1. Introduction

2. Drug Delivery Systems: Concepts and Characteristics of Lipid Nanocarriers

3. Strategies for Targeted Drug Delivery in Cancer

4. Conclusions

Acknowledgments

Chapter 19: Nanoparticles for magnetic hyperthermia

Abstract

1. Magnetic Hyperthermia in Cancer Therapy

2. Clinical Constraints

3. Magnetic Fluid Hyperthermia

4. Mechanisms of Heat Dissipation

5. Nanoparticles Synthesis and Coating

Acknowledgments

Chapter 20: Nanotechnology: a challenge in hard tissue engineering with emphasis on bone cancer therapy

Abstract

1. Introduction

2. Representative Materials for Hard Tissue Engineering

3. Drug Delivery Systems Designed for Hard Tissue Engineering

4. Conclusions

Acknowledgments

Chapter 21: Combination therapy of macromolecules and small molecules: approaches, advantages, and limitations

Abstract

1. Introduction

2. Peptides and Proteins as Therapeutic Agents in Cancer

3. Proteins as Targeting Agents in Cancer

4. Nucleic Acid-Based Macromolecule Therapeutics

5. Conclusions

Chapter 22: Nanosized drug delivery systems as radiopharmaceuticals

Abstract

1. Introduction

2. Future Perspectives

Chapter 23: Mesoporous silica nanoparticles: a promising multifunctional drug delivery system

Abstract

1. Introduction

2. Types and Synthesis of Mesoporous Silica Nanoparticles

3. Surface Functionalization of Mesoporous Silica Nanoparticles

4. Therapeutic Applications of MSNPs

5. Biological Performance of MSNPs

6. Characterization of MSNPs

7. Conclusion

Chapter 24: Cancer therapies based on enzymatic amino acid depletion

Abstract

1. Introduction

2. Amino Acid Deprivation Enzymes

3. Conclusions

Acknowledgments

Chapter 25: Self-emulsifying delivery systems: one step ahead in improving solubility of poorly soluble drugs

Abstract

1. Introduction

2. Various Formulation Strategies to Enhance Solubility and Permeability

3. Self-Emulsifying Drug Delivery System

4. Lipid Formulations (Charman et al., 1992; Colin, 2000; Collin, 1997; Pouton, 2000; Pouton and Porter, 2008)

5. Type of Spontaneously Emulsifying System (SEDDS)

6. Structure of SEDDS

7. Theories and Thermodynamics of Microemulsion Formulation

8. Difference Between SMEDDs and SNEDDs

9. Factors to be Consider for the Development of SEDDS

10. Suitable Drug Candidate Identification for SEDDS (Gursoy and Benita, 2004)

11. Composition of SEDDS

12. Formation of SEDDS

13. Construction of Phase Diagram (Aungst et al., 1993; Colin, 2000; Collin, 1997; Patel et al., 2008; Sahji, 2010; Singh et al., 2009b)

14. Mechanism of Self-Emulsification

15. Factors Affecting Formation of Microemulsion (Adhvait, 2010; Bhupinder et al., 2013; Khan et al., 2012; Patil and Paradkar, 2004; Tatyana, 2000)

16. Absorption Mechanism for Self-Microemulsification (Colin, 2008; Gupta et al., 2013; Pouton and Porter, 2008; Tatyana, 2000)

17. Biopharmaceutical Issues in the Selection of SEDDS

18. Advantages

19. Disadvantages (Chavda et al., 2012; Chavda, 2013; Colin, 2008; Muzaffar et al., 2013)

20. Evaluation

21. Applications

22. Advancement in Self-Emulsifying Systems

23. Marketed Formulation of SMEDDS

24. Recent Patents on Advanced Self-Emulsifying Systems

25. Conclusions

Chapter 26: Near-infrared light-responsive nanotherapeutic agents: application in medical oncology

Abstract

1. Introduction

2. Near-Infrared Light-Responsive Nanomolecule and Its Application in Medicine

3. Using Near-Infrared Light-Responsive Nanomolecule in Medical Oncology

4. Safety Consideration in Using Near-Infrared Light-Responsive Nanomolecule in Medical Oncology

5. Conclusions

Chapter 27: Current aspects of breast cancer therapy and diagnosis based on a nanocarrier approach

Abstract

1. Introduction

2. Nanosystems Containing Anticancer Agents Used for Metastatic Breast Cancer: Current Clinical Practice and Trial Studies

3. Use of Selective Biomarkers for Breast Cancer Detection, Analysis, Diagnosis, and Therapeutic Intervention

4. Overcoming Breast Cancer Drug Resistance

5. Conclusions

Acknowledgment

Chapter 28: Natural plant-derived anticancer drugs nanotherapeutics: a review on preclinical to clinical success

Abstract

1. Introduction

2. Plants as Source of Anticancer Agents

3. Physicochemical and Biopharmaceutical Limitations of Plant-Derived Anticancer Drugs

4. Nanomedicines in Cancer

5. Preclinical or Clinical Status of Plant-Derived Natural Anticancer Nanomedicines

6. Conclusions

Chapter 29: Nanotherapy: a next generation hallmark for combating cancer

Abstract

1. Introduction

2. Nanotechnology in Cancer and Treatment

3. Conclusions and Final Remarks

Acknowledgments

Chapter 30: Nanostructures for cancer therapy: from targeting to selective toxicology

Abstract

1. Introduction

2. Targeted Cancer Therapies

3. Nanoparticles Used in Cancer Therapy

4. Toxicological Aspects of Nanoscale Drug Delivery Systems

5. Conclusions

Acknowledgments

Index

Copyright

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List of Contributors

Delia Albuleţ,     University Politehnica of Bucharest, Bucharest, Romania

André F. Alves,     University of Lisbon, Lisbon, Portugal

Tatiana Andreani

University of Trás-os Montes and Alto Douro (UTAD)

Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Vila Real, Portugal

Ecaterina Andronescu,     University Politehnica of Bucharest, Bucharest, Romania

Gabriel-Cristian Anton,     University Politehnica of Bucharest, Bucharest, Romania

Fatemeh Atyabi,     Nanotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran

Kanhu C. Barick,     Bhabha Atomic Research Centre, Mumbai, Maharashtra, India

Bishnu P. Bastakoti

The University of Sydney, Darlington, NSW, Australia

Harvard University, Cambridge, MA, United States

Marta Benito,     Salud San Rafael Nebrija Science University Centre, University Camplutense of Madrid, Madrid, Spain

Jayita Bhattacharjee,     Bhabha Atomic Research Centre, Mumbai, Maharashtra, India

María D. Blanco,     University Camplutense of Madrid, Madrid, Spain

Bianca Boarca,     University Politehnica of Bucharest, Bucharest, Romania

Alexandra Bolocan

Emergency University Hospital

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Denisa-Andreea Bontas,     University Politehnica of Bucharest, Bucharest, Romania

Andreea Călugăreanu,     Elias University Emergency Hospital, Bucharest, Romania

Maria Deus Carvalho,     University of Lisbon, Lisbon, Portugal

Nuno M.F.S.A. Cerqueira,     University of Porto, Porto, Portugal

Ramesh Chandra,     University of Delhi, New Delhi, Delhi, India

Vivek P. Chavda,     Intas Biopharmaceuticals Ltd., Opp. Zydus Research Center, Moraiya, Ahmedabad, India

Mariana C. Chifiriuc,     Research Institute of the University of Bucharest (ICUB), Bucharest, Romania

Young W. Choi,     Chung-Ang University, Seoul, Korea

James C.L. Chow

Princess Margaret Cancer Centre, University Health Network

University of Toronto, Toronto, ON, Canada

M. Luísa Corvo,     Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal

Maria Margarida Cruz,     University of Lisbon, Lisbon, Portugal

Luciana M. de Hollanda,     University of Tiradentes (Unit) and Institute of Technology and Research (ITP), Aracaju, Brazil

Bilal Demir,     Ege University, Izmir, Turkey

Dilek Odaci Demirkol,     Ege University, Izmir, Turkey

Lia M. Ditu,     Research Institute of the University of Bucharest (ICUB), Bucharest, Romania

Gabriela Dorcioman,     National Institute for Lasers, Plasma, and Radiation Physics, Ilfov, Romania

Nelson Duran,     Chemistry Institute, University Estadual de Campinas, Campinas, Sao Paulo, Brazil

Henrique S. Fernandes,     University of Porto, Porto, Portugal

Pedro A. Fernandes,     University of Porto, Porto, Portugal

Liliana P. Ferreira

University of Lisbon, Lisbon

University of Coimbra, Coimbra, Portugal

Paula Ferreira,     CICECO - Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal

Anton Ficai,     University Politehnica of Bucharest, Bucharest, Romania

Denisa Ficai,     University Politehnica of Bucharest, Bucharest, Romania

Denisa A. Florea,     University Politehnica of Bucharest, Bucharest, Romania

Oana Fufă

University Politehnica of Bucharest, Bucharest

National Institute for Laser, Plasma and Radiation Physics, Măgurele, Romania

Ahmed Galal,     Tanta University, Tanta, Egypt

Rogério Gasar,     Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal

Irina Gheorghe,     Research Institute of the University of Bucharest (ICUB), Bucharest, Romania

Tudor G. Gherasim,     National Institute of Neurology and Neurovascular Diseases, Bucharest, Romania

Margarida Godinho,     University of Lisbon, Lisbon, Portugal

Shilpa C. Godiyal,     Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai, Maharashtra, India

Alexandru M. Grumezescu,     University of Bucharest, Bucharest, Romania

Valentina Grumezescu

National Institute for Lasers, Plasma, and Radiation Physics, Ilfov

University Politehnica of Bucharest, Bucharest, Romania

Bahar Guler,     Ege University, Izmir, Turkey

Emine Guler,     Ege University, Izmir, Turkey

Mine Silindir-Gunay,     Hacettepe University, Sihhiye, Ankara, Turkey

Indarchand Gupta,     Institute of Science, Aurangabad, Maharashtra, India

Puthusserickal A. Hassan

Bhabha Atomic Research Centre

Homi Bhabha National Institute, Mumbai, Maharashtra, India

Ivan Hevus,     North Dakota State University, Fargo, ND, United States

Alina M. Holban

University Politehnica of Bucharest, Bucharest, Romania

Research Institute of the University of Bucharest (ICUB), Bucharest, Romania

Avinash P. Ingle,     SGB Amravati University, Amravati, Maharashtra, India

Kisan R. Jadhav,     Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai, Maharashtra, India

Upendra K. Jain,     Chandigarh College of Pharmacy, Mohali, Punjab, India

Vilasrao J. Kadam,     Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai, Maharashtra, India

Min H. Kang,     Chung-Ang University, Seoul, Korea

Amanpreet Kaur,     Chandigarh College of Pharmacy, Mohali, Punjab, India

Fatemeh Khonsari,     Tehran University of Medical Sciences, Tehran, Iran

Ananiy Kohut,     Lviv Polytechnic National University, Lviv, Ukraine

Zongwen Liu,     The University of Sydney, Darlington, NSW, Australia

Jitender Madan,     Chandigarh College of Pharmacy, Mohali, Punjab, India

Sabyasachi Maiti,     Gupta College of Technological Sciences, Asansol, West Bengal, India

Avudaiappan Maran,     Mayo Clinic, Rochester, MN, United States

Hodorogea Maricica,     University Politehnica of Bucharest, Bucharest, Romania

H. Susana Marinho,     Centro de Química e Bioquímica (CQB), Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal

Ana M. Martínez

University Francisco de Vitoria

University Camplutense of Madrid, Madrid, Spain

M. Bárbara F. Martins,     Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal

Wanessa S.G. Medina,     Faculdades Integradas Padre Albino (FIPA), Catanduva, São Paulo, Brazil

Alina Melinescu,     University Politehnica of Bucharest, Bucharest, Romania

Livia P. Mendes

Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, United States

CAPES Foundation, Ministry of Education of Brazil, Brasilia, Federal District, Brazil

Sofia G. Mendo,     University of Lisbon, Lisbon, Portugal

Mara M. Mihai,     Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Fatemeh Mottaghitalab,     Nanotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran

Irina Negut

National Institute for Lasers, Plasma, and Radiation Physics

University Politehnica of Bucharest, Bucharest, Romania

Mariana S. Oliveira,     Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil

Olguţa A. Orzan,     Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

A. Yekta Ozer,     Hacettepe University, Sihhiye, Ankara, Turkey

Ravi S. Pandey,     Guru Ghasidas University, Bilaspur, Chhattisgarh, India

Konstantinos Pantapasis,     University Politehnica of Bucharest, Bucharest, Romania

Priti P. Pednekar,     University of the Sciences, Philadelphia, PA, United States

Elena Pérez,     University Camplutense of Madrid, Madrid, Spain

Magdalena Plebanski,     Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Melbourne, VIC, Australia

Roxana C. Popescu

University Politehnica of Bucharest, Bucharest, Romania

Horia Hulubei National Institute for Physics and Nuclear Engineering, Măgurele, Romania

Fabíola S.G. Praça,     University of São Paulo, São Paulo, São Paulo, Brazil

Mahendra Rai,     SGB Amravati University, Amravati, Maharashtra, India

Rukkumani Rajagopalan

Pondicherry University, Kalapet, Puducherry

University of Madras, Chennai, Tamil Nadu, India

Tudor Raluca,     University Politehnica of Bucharest, Bucharest, Romania

Maria J. Ramos,     University of Porto, Porto, Portugal

Suman Rana

Bhabha Atomic Research Centre

Homi Bhabha National Institute, Mumbai, Maharashtra, India

Nehal Salahuddin,     Tanta University, Tanta, Egypt

Antonello Santini,     University of Napoli Federico II, Naples, Italy

Daniela Sarghiuta,     University Politehnica of Bucharest, Bucharest, Romania

Cordelia Selomulya,     Faculty of Engineering, Clayton, VIC, Australia

Patrícia Severino,     University of Tiradentes (Unit) and Institute of Technology and Research (ITP), Aracaju, Brazil

Akram Shafiee,     Tehran University of Medical Sciences, Tehran, Iran

Dhaval Shah,     Maharaja Sayajirao University, Baroda, Gujarat, India

Ankita Sharma,     Chandigarh College of Pharmacy, Mohali, Punjab, India

Amélia M. Silva

University of Trás-os Montes and Alto Douro (UTAD)

Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Vila Real, Portugal

Eliana B. Souto,     REQUIMTE/LAQV, Group of Pharmaceutical Technology, University of Coimbra, Coimbra, Portugal

Selma B. Souto,     Hospital of Braga, Braga, Portugal

Carla S. Silva Teixeira,     University of Porto, Porto, Portugal

Suna Timur,     Ege University, Izmir, Turkey

Vladmir P. Torchilin,     Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, United States

Peter Tsirikis,     Faculty of Engineering, Clayton, VIC, Australia

Kumari Varsha,     Chandigarh College of Pharmacy, Mohali, Punjab, India

Monica Vazzana,     University of Messina, Messina, Italy

Gunjan Verma,     Bhabha Atomic Research Centre, Mumbai, Maharashtra, India

Lamaru Victor,     University Politehnica of Bucharest, Bucharest, Romania

Ologeanu Vlad,     University Politehnica of Bucharest, Bucharest, Romania

George M. Vlasceanu,     University Politehnica of Bucharest, Bucharest, Romania

Andriy Voronov,     North Dakota State University, Fargo, ND, United States

Stanislav Voronov,     Lviv Polytechnic National University, Lviv, Ukraine

Viroj Wiwanitkit

Hainan Medical University, Haikou Shi, Hainan Sheng, China

University of Nis, Nis, Serbia

Joseph Ayobabalola University, Ikeji-Arakeji, Osun, Nigeria

Dr DY Patil Medical University, Pune, Maharashtra, India

Surin Rajabhat University, Surin, Thailand

Sue D. Xiang,     Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Melbourne, VIC, Australia

Jatinder V. Yakhmi,     Homi Bhabha National Institute, Mumbai, Maharashtra, India

Michael J. Yaszemski,     Mayo Clinic, Rochester, MN, United States

Ho Y. Yoon,     Chung-Ang University, Seoul, Korea

Forouhe Zahir,     Tehran University of Medical Sciences, Tehran, Iran

Foreword of the Series

Material science and engineering at the nanoscale has brought revolutionary advances to the biomedical sciences, overturning many of the traditionally known approaches. Nanotechnology has driven many of the most successful innovative technologies, and the impressive record of accomplishments in the field make nanostructures promising candidates for medical therapy applications. The advantages that nanomaterials have already provided to therapeutics, such as targeted and controlled delivery, wide accessibility, high specificity, low side effects, improved efficiency, and impressive versatility are currently considered key elements in designing personalized medicine approaches for prophylaxis, diagnosis, and therapy.

Therapeutic nanostructures can be greatly diverse, and their unique properties have led to the development of highly specialized biosensors, more efficient drug delivery vehicles, and controlled release targeting systems to fight severe or incurable diseases, such as cancer, infections, and cardiovascular disease.

In view of the astounding progress made in the field of therapeutic nanotechnology and its rapidly progressing expansion, this book aims to collect in one place all the recent and most innovative aspects of nanomaterials in both current and future therapy. The series is organized into five volumes, covering the main areas that are relevant for the design and implementation of nanostructures in medical therapies.

The first volume, Nanostructures for Novel Therapy: Synthesis, Characterization, and Applications, describes methods to obtain and characterize nanosystems, emphasizing their biomedical applications. Special attention is paid in this volume to modern synthesis methods to reduce side effects and limit the toxicity of nanomaterials in biomedical applications. Numerous examples of nanostructures designed for therapy, as well as the most efficient synthesis and characterization routes for these materials, are clearly described and critically analyzed.

The second volume, entitled Nanostructures for Drug Delivery, covers one of the most widely utilized and investigated applications of nanomaterials in the biomedical field, namely, drug delivery. Designing nanostructures to specifically and safely carry therapeutic agents to their final destination is an intriguing approach to future targeted therapies. This approach could provide a treatment for previously incurable diseases, as well as reducing the side effects of current drugs. Many highly active drugs are severely limited by side effects related to their unspecific sites of action. This volume introduces the readers to the amazing field of nanomedicine by discussing the versatility and variety of nanovehicles for drug delivery and targeting. Moreover, readers will find numerous examples and will learn about the currently used or investigational drug delivery agents for therapy, prophylaxis, and diagnosis.

Volume 3, Nanostructures for Antimicrobial Therapy, highlights the impressive progress made by nanotechnology in the design of novel antimicrobial approaches. Since microbial resistance to antibiotics is a real and increasingly worrying issue across all countries, the development of more efficient antimicrobial agents to provide control of future infections is at a high priority. Antimicrobial nanosystems have proved to be remarkably efficient against drug-resistant microorganisms, plus they are able to fight biofilm-associated infections and can control the social behavior of microbial communities. Nanostructures can also reduce microbial virulence factors and reduce pathogenesis mechanisms, offering a promising alternative for future therapy.

Volume 4, entitled Nanostructures for Cancer Therapy, covers the applications of nanomedicine in cancer diagnosis and treatment. The use of nanoparticles for cancer therapy is not in itself a new approach, but numerous recent advances have been made in this area. The aim of this volume is to cover the most interesting new approaches in the management of this deadly disease. Nanosized drugs are currently believed to represent the most efficient approach in cancer chemotherapy, and this volume provides coverage of the latest and most novel findings, while also discussing possible improvements in more established types of nanosystems that can increase the efficiency of cancer therapy.

The final volume of this series, entitled Nanostructures for Oral Medicine, covers the progress made in applications of nanotechnology in treating various diseases of the oral cavity, as well as progress in nanotechnology applications in dentistry. Readers can learn about the most efficient modern materials used to treat or to prevent widely encountered oral diseases, such as gingivitis, periodontitis, caries, and dental plaque. Moreover, restorative dentistry also now makes wide use of nanomaterials.

Overall, this book series provides a state-of-the-art compendium of knowledge, and a crystal ball for seeing into the future of biomedical nanotechology and nanomedicine. It has an appeal for researchers, clinicians, engineers, pharmacologists, pharmacists, oncologists, infectious disease experts, and dentists. In addition, interested general readers will discover the impact, current progress, and future applications of nanotechnology in therapeutics and diagnosis. Taken together, nanoscale approaches will improve the efficiency of personalized medicine for better management of diseases in the 21st century.

Michael R. Hamblin

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, United States

Department of Dermatology, Harvard Medical School, Boston, MA, United States

Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States

Preface

About the Series (Volumes I–V)

In our permanently changing world, novel therapeutics are constantly required to manage health and well-being of population. Although numerous diseases are currently considered incurable, massive progress made in biomedicine and associated fields, such as chemistry, physics, engineering, pharmacology, and materials science offers a new light to the therapeutics domain. In this context, most physicists and researchers believe that a personalized and adequate treatment may significantly improve the outcome of severe diseases and ensure a faster healing. Nanotechnology offers great perspectives for personalized medicine because nanostructured therapeutics proved their efficiency and amazing impact in improving therapy, prophylaxis, and diagnosis. The emerging field of nanosized materials has numerous applications in the biomedical field, especially in therapy. This series of five volumes came out by the need of learning about recent progress of the science of nanostructured materials to improve current therapy and lead to the next level. The books offer an interesting and updated perspective regarding applications of nanomaterials in therapy of most investigated and difficult-to-treat diseases, such as cancer and severe infections. The presentation approach of each chapter contained in those five volumes is clear and easy to understand by readers and particularly interesting for biomedical specialists, researchers, and engineers. The series is organized in an attractive manner for students and academics on the field, starting with a volume dealing with synthesis, characterization, and main applications of nanostructures, emphasizing on their impact in therapy. Next volume reveals the most recent progress made on a very investigated field, considered a key element in personalized medicine and future therapy, namely nanostructured drug delivery systems. Their impact in antimicrobial therapy is also widely discussed, and suggestive examples are given and explained. Moreover, a whole volume is dedicated to the management of the disease of the century—cancer—revealing the huge value added by the utilization of nanosystems in the therapy of this deadly disease. Important aspects related to improved diagnosis and prophylaxis are highlighted. In the last volume, the progress and novel applications of nanotechnology in oral medicine is dissected. The field of oral diseases represents an interesting and a priority field because both physicists and researchers believe that they can be prevented and treated more easily with targeting systems and nanofunctional prosthetics. All chapters are clearly illustrated to highlight important or more difficult-to-understand aspects, and suggestive examples are often enumerated in organized tables, which are explained and discussed. Overall, the series contains very recent but accessible and interesting information regarding the progress of nanostructures in therapeutics and gives a novel perspective about future therapy of severe diseases.

Alexandru M. Grumezescu

University Politehnica of Bucharest, Bucharest, Romania

About Volume IV

The fourth volume of the series Therapeutic Nanostructures is entitled Nanostructures for Cancer Therapy. As cancer represents the disease of the century, numerous efforts are being made to limit its consequences. Starting with the development of extremely sensitive detection kits able to sense just a few malignant cells, and ending with specialized therapeutic agents capable of specifically targeting tumors without harming healthy tissue, nanomaterials have found numerous applications in the management of this highly life-threatening condition. The design of specialized nanosensors applied for early diagnosis of tumors is considered one of the most efficient among biomedical innovations. Early and correct diagnosis is crucial to increase the outcome of the therapy; therefore, progress made in diagnosis and prophylaxis represents another important step forward for the applicative field of biomedical nanomaterials. The design of innovative and more efficient anticancer nanostructured drugs represents the main focus of this volume. Recent progress, along with relevant challenges, proposed solutions, and current limitations of nanotechnology in the development of anticancer agents are discussed and numerous examples are given. Volume IV contains 30 chapters prepared by outstanding international researchers from the USA, Canada, Italy, Romania, Turkey, Egypt, Iran, India, Korea, Portugal, Brazil, Australia, Spain, Ukraine, Portugal, and Thailand.

In Chapter 1, entitled Nanotechnology for Personalized Medicine: Cancer Research, Diagnosis, and Therapy, Delia Albuleţ et al. summarize the types of nanotechnologies that have made a great impact in medicine and especially in cancer research and therapy. Using drug delivery systems based on liposomes, magnetic nanoparticles, noble metal nanoparticles, polymeric nanoparticles, upconversion nanoparticles, quantum dots, or carbon nanomaterials, a new perspective in curing cancer is given.

Konstantinos Pantapasis et al., in Chapter 2, entitled Bioengineered Nanomaterials for Chemotherapy, presents the most investigated nanomaterials currently under consideration for anticancer approaches, along with essential information regarding their synthesis properties and most recent applications.

Chapter 3, prepared by Emine Guler et al., entitled Biofunctionalized Nanomaterials for Targeting Cancer Cells, gives an up-to-date overview about the most recently developed nanomaterials and the loadings of nanomaterials with various drugs to prepare nanocarrier systems, as well as the usage of the obtained nanobiomaterials in targeting cancer cells.

In Chapter 4, entitled Improving Chemotherapy Drug Delivery by Nanoprecision Tools, Nehal Salahuddin and Ahmed Galal discuss various aspects of nanoparticles, including polymer nanoparticles, inorganic nanoparticles, polymer/inorganic nanocomposites, formulation, characterization, and the effect of their characteristics and morphologies on their applications in delivery of chemotherapy drug molecules, including the advantages, disadvantages, and challenges facing nanomedicine in oncology.

In Chapter 5, entitled RIPL Peptide as a Novel Cell-Penetrating and Homing Peptide: Design, Characterization, and Application to Liposomal Nanocarriers for Hepsin-Specific Intracellular Drug Delivery, prepared by Min H. Kang et al., along with a brief introduction of cell-penetrating and homing peptides, important aspects in the design of specific peptides and targetable liposomal nanocarriers are discussed, focusing on hepsin-specific intracellular drug delivery.

Chapter 6, entitled Progress of Nanoparticles Research in Cancer Therapy and Diagnosis, prepared by Irina Negut et al., reviews the novel applications of magnetic nanoparticles as drug nanocarriers for the therapy of different oncological diseases, together with imaging characteristics that recommend them as efficient contrast agents in magnetic resonance imaging applications.

Suman Rana et al., in Chapter 7, entitled Interfacial Engineering of Nanoparticles for Cancer Therapeutics, focus on recent developments in the area of surface modification of inorganic and organic nanoparticles for selective delivery of anticancer drugs. Various examples of applications of liposomes, micelles, vesicles, hydrogels, and protein and polymer nanoparticles, as well as the nanoparticles of metals, metal oxides, and their hybrid structure as efficient carriers of anticancer drug are briefly dissected.

Rukkumani Rajagopalan and Jatinder V. Yakhmi, in Chapter 8, entitled Nanotechnological Approaches Toward Cancer Chemotherapy, present an in-depth insight into the delivery and economic aspects of biodegradable and nonbiodegradable nanoparticles, and discuss the gaps that exist between lab-scale and commercial potential of therapy using them.

Tatiana Andreani et al., in Chapter 9, Cancer Therapies: Applications, Nanomedicines and Nanotoxicology, highlight the benefits of nanotechnology and of nanomedicines for cancer diagnosis and therapy, focusing on the relevant aspects of nanotoxicology.

Bishnu P. Bastakoti and Zongwen Liu, in Chapter 10, entitled Multifunctional Polymeric Micelles as Therapeutic Nanostructures: Targeting, Imaging, and Triggered Release, address the current status and possible future direction of the highly emerging area of multifunctional nanocarriers based on micelles of different block copolymers with controlled loading, targeting, imaging, and triggered release.

Chapter 11, prepared by Mara M. Mihai et al., entitled Recent Advances in Diagnosis and Therapy of Skin Cancers Through Nanotechnological Approaches, offers an up-to-date overview about medical nanotechnology and the ability of nanoscale materials to overcome major limitations of current therapeutic strategies in skin cancer by specifically targeting the tumor, by stabilizing chemotherapeutic compounds, and by ensuring a controlled and durable release of the drug. Moreover, due to special particularities of nanoparticles and complex nanosystems, they can be efficiently utilized for skin tumor detection in a fast and secure manner, nanoparticles being able to penetrate and be detected even in the deepest layers of the skin.

Chapter 12, prepared by Peter Tsirikis et al., entitled Design of Nanoparticle Structures for Cancer Immunotherapy, examines how prophylactic and therapeutic tumor immunities can be achieved using nanoparticles targeting dendritic cells in vivo. Moreover, this review elucidates the differential immunological properties of engineered nanoparticles. Surface morphology, size, shape, and surface functionalization can influence cellular uptake, toxicity, immunogenicity, and the T-helper 1 (Th1)/T-helper 2 (Th2) bias of the immune response.

Chapter 13, entitled Recent Advances of Folate-Targeted Anticancer Therapies and Diagnostics: Current Status and Future Prospectives, prepared by Ana M. Martínez et al., focuses on the possibilities offered by folic acid toward recent advances in cancer treatment and diagnostics, and also future perspectives on these folate-targeted therapies to fight against cancer with more efficient prophylaxis.

In Chapter 14, Anticancer Efficiency of Curcumin-Loaded Invertible Polymer Micellar Nanoassemblies, Ivan Hevus et al. present a new approach in polymer-based delivery of poorly water-soluble drugs. Also, the authors give an overview regarding the administration of curcumin using polymer micelle assemblies.

Chapter 15, prepared by James C. L. Chow, entitled Dose Enhancement Effect in Radiotherapy: Adding Gold Nanoparticles to Tumor in Cancer Treatment, offers recent insights about gold nanoparticle-enhanced radiotherapy. Also, the authors discuss the physical and radiobiological effects on the cancer cell killing in the presence of gold nanoparticles.

Oana Fufă et al., in Chapter 16, entitled Silver-Based Nanostructures for Cancer Therapy, give an overview regarding the latest results reported in novel silver-based nanotechnology-derived systems as promising strategies for modern cancer therapy.

Sabyasachi Maiti, in Chapter 17, Ligand-Decorated Polysaccharide Nanocarriers for Targeting Therapeutics to Hepatocytes, emphasizes on the synthesis of ligand-polysaccharide nanocarriers and recent trends in ligand-directed therapeutic strategies for curing liver diseases.

Chapter 18, entitled Targeted Delivery of Anticancer Drugs: New Trends in Lipid Nanocarriers, prepared by Mariana S. Oliveira et al., presents the recent progress about targeted delivery of anticancer drugs. Stimuli-sensitive and combination therapies and their advantages are discussed, with particular attention given to lipid-based nanocarriers. The authors focus on liposomes, lipid-based micelles, and the emerging class of particles based on lipid components other than phospholipids, including solid lipid nanoparticles and nanostructured lipid carriers.

Maria M. Cruz et al., in Chapter 19, entitled Nanoparticles for Magnetic Hyperthermia, present a general view of the different aspects involved in the research on nanoparticles for magnetic hyperthermia therapeutics. The recent developments to improve the nanoparticles’ ability to act as nanoheaters, namely, new synthesis methods to obtain ferrite nanoparticles and core@shell nanostructures (with different magnetic phases), are discussed, together with the hyperthermia efficiency results.

Chapter 20, prepared by Denisa Ficai et al., entitled Nanotechnology: A Challenge in Hard Tissue Engineering with Emphasis on Bone Cancer Therapy, presents recent progress about the role of nanotechnology in developing materials for hard tissue engineering with a special attention in bone cancer therapy. Based on the recent advances in the field of materials, the most promising material for bone tissue regeneration seems to be the tissue-engineered nanocomposites, which can be designed to achieve specific functionalities.

Forouhe Zahir et al., in Chapter 21, entitled Combination Therapy of Macromolecules and Small Molecules: Approaches, Advantages, and Limitations, discuss the utilization of macromolecules consisting of peptides, antibodies, and nucleic acids as novel therapeutic agents in cancer treatment. The first part summarizes several signaling pathways involved in cancer generation and progression, and approved and in-trial monoclonal antibodies related to everyone. In the second part, targeting approaches to cancer cells are discussed. Finally, different classes of nucleic acids consisting of antisense oligonucleotides, RNA ribozymes, RNAi, and aptamers are introduced.

Chapter 22, prepared by Mine S. Gunay and Yekta A. Ozer, entitled Nanosized Drug Delivery Systems as Radiopharmaceuticals, presents an up-to-date review about the utilization of nanosized, specifically targeted drug delivery systems for both diagnosis and therapy of several diseases as theranostics.

Chapter 23, entitled Mesoporous Silica Nanoparticles: A Promising Multifunctional Drug Delivery System, prepared by Priti P. Pednekar et al., addresses the synthesis, characterization, advantages, as well as applications of mesoporous silica nanoparticles in the delivery of anticancer drugs.

Chapter 24, prepared by Carla Teixeira et al., entitled Cancer Therapies Based on Enzymatic Amino Acid Depletion, reviews the structure, function, catalytic mechanism, and therapeutic application of some amino acid–depriving enzymes. Particular attention is given to enzymes that have potential or are currently used in the treatment of several types of cancer, namely: (1) l-asparaginase, used for the treatment of acute lymphoblastic leukaemia; (2) l-arginase and l-arginine deiminase, used in the therapy of hepatocellular carcinomas and melanomas, two diseases that account annually for approximately 1 million new cases and for which there is currently no efficacious treatment; and (3) l-methioninase, with potential to be used in the treatment of breast, colon, lung, and renal cancers.

Vivek P. Chavda and Dhaval Shah, in Chapter 25, entitled Self-Emulsifying Delivery Systems: One Step Ahead in Improving Solubility of Poorly Soluble Drugs, discuss the lower bioavailability of drugs and the use of a lipid formulation classification system combined with appropriate in vitro tests that help to establish a database for in vitro–in vivo correlation studies. Certain disadvantages associated with conventional self-emulsifying drug delivery systems are now overcome by some of the recent advancements that are described in this chapter along with recent patents in such fields.

Chapter 26, entitled Near-Infrared Light-Responsive Nanotherapeutic Agents: Application in Medical Oncology, prepared by Viroj Wiwanitkit, details and discusses the application of new nanomolecules, namely near-infrared light-responsive agents, with applications in both diagnostic and therapeutic medical oncology.

Fabíola S.G. Praça et al., in Chapter 27, entitled Current Aspects of Breast Cancer Therapy and Diagnosis Based on a Nanocarrier Approach, review nanosystems containing anticancer agents that are used for metastatic breast cancer in clinical practice, clinical trials, and research orientations. Also, the authors provide an overview of biomarkers used in metastatic breast cancer allowing for improved prognosis and therapy.

Chapter 28, prepared by Kumari Varsha et al., Natural Plant-Derived Anticancer Drugs Nanotherapeutics: A Review on Preclinical to Clinical Success, provides an overview of the plant-originated anticancer drug nanomedicines currently undergoing preclinical or clinical trials or being used in clinics. Special emphasis is given on the elucidation of anticancer and antiangiogenic mechanisms of action of natural anticancer drugs. Moreover, attention has also been paid to passive and active targeting achieved in natural anticancer drugs by using colloidal and nanoparticulate systems–based nanomedicines.

Chapter 29, prepared by Avinash P. Ingle et al., entitled Nanotherapy: A Next Generation Hallmark for Combating Cancer, gives an overview about the role of nanotechnology in the form of drug delivery systems with nanoparticles (i.e., nanotherapy that shows a vast potential for cancer treatments). Nanotherapy is an actual modern mode of treatment that can be applied for cancer therapy with few or no side effects.

Chapter 30, entitled Nanostructures for Cancer Therapy: From Targeting to Selective Toxicology, by George M. Vlasceanu et al., presents an up-to-date overview about one of the most controversial cancer treatments: targeted cancer therapy. Even though nanostructures may offer a great advantage in cancer therapy, numerous toxicity-related aspects should still be considered to implement the use of anticancer nanosystems in current cancer treatment.

Anton Ficai

University Politehnica of Bucharest, Bucharest, Romania

Alexandru M. Grumezescu

University Politehnica of Bucharest, Bucharest, Romania

Chapter 1

Nanotechnology for personalized medicine: cancer research, diagnosis, and therapy

Delia Albuleț*

Denisa A. Florea*

Bianca Boarca*

Lia M. Ditu**

Mariana C. Chifiriuc**

Alexandru M. Grumezescu*

Ecaterina Andronescu*

*    University Politehnica of Bucharest, Bucharest, Romania

**    Research Institute of the University of Bucharest (ICUB), Bucharest, Romania

Abstract

Despite huge economical and scientific effort, cancer still remains one of the leading causes of mortality and morbidity, affecting human population at any age. Here we summarize the types of nanotechnologies that made a great impact in medicine and especially in cancer research and therapy. Using drug delivery systems based on liposomes, magnetic nanoparticles, noble metal nanoparticles, polymeric nanoparticles, upconversion nanoparticles, quantum dots, or carbon nanomaterials gives scientists a new hope of finding solutions for curing cancer. This approach brings a new perspective for the research, diagnosis, and treatment of cancer through the implementation of a new concept—personalized medicine—which has the potential to offer an efficient cure for virtually any type of malignancy.

Keywords

personalized cancer therapy

drug delivery

nanodrugs

targeting

nanoparticles

Chapter Outline

1 Introduction

2 Main Types of Cancer

3 Personalized Treatment of Cancer

3.1 Nanotechnology: Progress in Cancer Research

4 Nanotreatment of Cancer

5 Nanodrugs and Nanocarriers

5.1 Magnetic Nanoparticles

5.2 Noble Metal Nanoparticles

5.3 Upconversion Nanoparticles

5.4 Quantum Dots

5.5 Carbon-Based Nanostructures

5.6 Polymeric Nanoparticles

5.7 Liposomes

6 Conclusions

Acknowledgments

References

1. Introduction

Cancer represents an important health problem at a global level being the second cause of death in the United States. The American Cancer Society provides each year relevant data about the number of deaths caused by cancer, and it is believed that cancer-related deaths could surpass the number of deaths caused by heart diseases in the next years (Siegel et al., 2015). Cancer is a multistep process and appears as a consequence to the loss of control of cell division, leading to uncontrolled cellular proliferation (Bashyam, 2002), and also appears as the ability of the abnormal cells to overwhelm other tissues (Aly, 2012).

The EUROCOURSE project developed a special program known as the European Cancer Observatory (ECO) to collect all the information available on cancer incidence, survival, prevalence, and mortality in Europe from 40 European countries, estimated for 2012. Based on this data, more than 3.3 million new cancer cases have been estimated, apart from nonmelanoma skin cancer. The widespread cancers were those of lung, prostate, large bowel, and breast, representing 1.7 million cases. The cancer with the greatest number of deaths is lung cancer, while the cancer with the greatest number of prevalent and incident cases is breast cancer (Steliarova-Foucher et al., 2015).

Normal cells become tumor cells through changes taking place in their DNA, under the pressure of the environmental factors that cause the initial mutation. Normally, when DNA sequences are injured, the cells activate their repair mechanism or, if the damages are too extensive, the cells die. The development of tumors derives from single modified cells that begin to proliferate abnormally because of the unrepaired DNA mutations. Tumor progression is viewed as a multistep process involving mutation and selection of cells with progressively increasing capacity for proliferation, survival, and invasion. One of the hallmarks of cancer is represented by the rapid growth of tumors, which leads to low oxygen rates (hypoxic conditions) (Blazejczyk et al., 2015).

Nowadays, the genomic alterations that lead to cancer are better understood and the connections between genes and the conditions of the human body have been studied to prevent cancer initiation.

The genes that cause tumor development under the mutation process are usually grouped in two main categories:

1. Cancer-promoting oncogenes, also known as protooncogenes, which are frequently activated in cancer cells, giving new properties, such as hyperactive division and growth, ability to become recognized in new tissues, or protection against apoptosis (programmed cell death).

2. Tumor suppressor genes (antioncogenes or TSG), which are inactivated in cancer cells (Aly, 2012; Harrington, 2011).

To develop a malign neoplasm, mutations in both types of genes are expected. Substances that can cause the DNA mutations (also known as carcinogens) are linked to specific types of cancer. For example, smoking is connected to lung cancer, and solar ultraviolet radiation may cause skin cancer.

The ability of abnormal cells to grow or spread to other vital organs is called metastasis and it is the most common cause of death for patients with malign neoplasm. The metastasis process takes place when the abnormal cells access the body’s blood vessels to move to other parts of the human body where they can proliferate and develop new tumors (Le Dévédec et al., 2010). Certainly, about 90% of malign neoplasm deaths come from metastasis (Ganapathy et al., 2015). At the beginning of the metastasis process, abnormal cells activate the epithelial-to-mesenchymal transition, also known as EMT, which refers to the activation of the latent embryonic program by the cancer cells (Pietilä et al., 2016).

Angiogenesis process involves the endothelial cells, which break free from the blood vessels and develop tubes during the proliferation process (Tsimberidou et al., 2015). The cancer cells located in tumors are an abundant resource of proangiogenic molecules that guide the activity of endothelial cells, promoting their migration and determination. The endothelial cells manage the activity of platelets and they have an antiinflammatory, anticoagulant, and antiadhesive phenotype. The structure of tumor vessels is correlated with the malignancy of the tumors because of the cancer cells that grow along the existing vessels (Blazejczyk et al., 2015).

The platelets are well known for their main function: to stop hemorrhage after tissue damage and vascular injury, because they have the ability to release bioactive factors when they become activated (when matrix is exposed or if inflammation appears and disturbs the endothelium) (Yan and Jurasz, 2015). Besides their function in hemostasis, activated platelets also contribute to tumor cell metastasis with an intense impact on circulating tumor cell survival, growth, and invasiveness. Their influence on abnormal cells is based on mechanisms such as the release of GFs (growth factors), proteins, and so on. The cancer cells have the ability to control the platelets function so as to improve their extravagation and development (Tesfamariam, 2016).

Disorder prevention is built around the idea that several risk factors may be controlled, for example, decreasing exposure to notorious causes of cancer, such as sunlight exposure, cigarettes, alcoholic drinks, unhealthy meals, and so on, or promoting activities that are correlated with reduced cancer risks (Bashyam, 2002; White et al., 2013).

In the past few years, the main role of numerous intracellular or extracellular biochemical signals in malign neoplasm cell proliferation, metastasis, and invasion has been revealed. The mechanical properties of the ECM (extracellular matrix) showed an important influence in the metastasis process. In vivo and in vitro tests showed that enhanced tissue rigidity has a functional role in controlling the malign character of a tumor and tumor invasion (Wei and Yang, 2015).

Solid tumors are living units made of various complex cell types that may even surpass the healthy tissues. According to Jiang et al. (2015), a new theory about the malignant progression of cancer was developed indicating the idea that this evolution not only depends on abnormal cells genetic aberrations, but also on the bidirectional dynamic and complex connections between stroma and cancer cells within the tumor microenvironment.

Breast, lung, and prostate cancer are among the most frequent forms of solid tumors. Cancerous cells found in solid tumors enroll inflammatory cells, producing inflammatory stroma. The invasiveness and the resistance of the metastatic breast cells are the result of the oncogenic epithelial to mesenchymal transition. In this case, cells undergoing EMT hit the nearby stroma causing the extravasations of cells in the blood, individually or as a mass (Subramanian et al., 2015).

The epithelium is a well-established structure with a uniform layer formed by the epithelial cells. In the case of the breast, these types of cells develop the lining of canals, which are responsible for milk transport in the lactation process. The most common type of carcinoma in breast cancer is the ductal carcinoma appearing both in men and women, but its prevalence in men is uncommon (Videira et al., 2014).

An important role in encouraging the proliferation process of both the neoplastic and the normal breast epithelium is given by estrogens (Russo and Russo, 2006). There are many types of physiological estrogens, such as estrogen, progesterone, cortisol, and aldosterone, but the main physiological estrogen in mammals is estradiol (E2) (Baker, 2013). Estradiol is the most biologically active hormone located in the breast tissue and it stimulates the breast evolution at puberty and during sexual maturity. In vivo and in vitro tests revealed the idea that E2 has the ability to induce full neoplastic transformation of epithelial cells (Russo and Russo, 2006).

A significant regulator in breast cancer is the extracellular matrix. It produces several modifications in organization and structure, in comparison to the mammary gland under homeostasis. A number of ECM elements play an important role in metastasis and progression of breast cancer, such as collagens, specific laminins, fibronectin, glycosaminoglycan, proteoglycans, and ECM remodeling enzymes.

Other common cell types that take part in tumor development are CAFs (cancer-associated fibroblasts, neuroendocrine cells, adipocytes) and MSCs (human mesenchymal cells or blood stem cells). These cells are located in the tumor microenvironment (TME). Additionally to cellular components, the TME is composed of a network of secreted proteins (which can change the extracellular matrix structure and composition) and biomechanical properties of the stromal tissue (Pietilä et al., 2016). A sustaining TME permits stromal cells to develop with cancer cells, encouraging the initial spreading. In contrast to cancer cells, stromal cells located inside the tumor microenvironment are genetically stable and this denotes a therapeutic target with a decreased risk of drug resistance (Chen et al., 2015).

Tissue regeneration and cancer are not restricted to ECM structure or composition, but also involves remodeling enzymes that can change the ECM in different ways. The remodeling enzymes can increase the cancer cell migration and invasion and can affect the biological function and properties of ECMs components. These factors contribute directly to the development of metastasis and progression of cancer (Insua-Rodríguez and Oskarsson, 2015).

2. Main Types of Cancer

Nowadays, a top killer in both women and men in the USA is lung cancer, with an approximate number of 160,000 deaths and 225,000 new cases in 2014, causing more deaths each year than the next main causes of malign neoplasm deaths (rectal/colon, prostate) and it is constantly associated with a history of about 20 years of consuming tobacco-based products. The main causes of this type of cancer initiation are: smoking, different chemicals, such as asbestos, nickel, uranium, family history, or radon gas.

There are two types of lung cancer: primary and secondary. The primary type refers to the moment when the tumor starts to increase in the lung first, and the secondary type is when the tumor has spread to the lung from other places or tissues. Primary lung cancer is divided into two principal categories: nonsmall cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) (Karachaliou et al., 2015). The most common lung cancer is the NSCLC and it presents several symptoms including anemia, paraneoplastic syndrome, weight loss, headaches, or bone pain. The SCLC type is extremely sensitive to initial therapy and most people diagnosed with this type of lung cancer die of recurrent disease. For patients with an extensive-stage diagnosis, chemotherapy can alleviate symptoms and extend survival, but even so long-term survival is uncommon. A great number of SCLC cases are connected to cigarette smoking (Kalemkerian et al., 2013).

The lung neoplasm is a rapidly metastasizing and prevalent cancer with a high potential of invasiveness. Numerous mechanisms take part in the cell transformation from normal to malignant, such as genetic and epigenetic alterations that promote the spread of cancer by clonal expansion. It is very important to detect and characterize these molecular changes to improve prevention, treatment, and early detection (Lemjabbar-Alaoui et al., 2015).

The lung cancer presents variable signs or symptoms and around 70% of patients detected with lung cancer show an advanced stage III or IV (Travis et al., 2013). There are several tests that may be done to diagnose lung malign neoplasm, for example, chest X-ray, lung biopsy, computed tomography scan, or bronchoscopy. When patients are diagnosed with stage IV they are frequently candidates for systemic therapy (which involves targeted therapy, chemotherapy, or a combination), palliative treatment, or clinical trials. The purpose is to detect patients with stage IV metastatic disease before they begin any aggressive treatment (like combined therapy) (Ettinger et al., 2012).

To reduce the risk of lung cancer initiation, there are a few things that may be done, such as quitting smoking, a rich fiber diet including fresh fruits and vegetables, and excluding fatty foods from the daily diet.

Prostate cancer is a common disease around the world with a high rate of mortality: it is the secondmost common cause of male death in the United Kingdom and it is expected to kill around 27,000 men in the USA. A percentage of 70% of patients with metastatic prostate malign neoplasm die from their disease within 5 years (Witte, 2016). This disease is extremely heterogeneous and it can vary from low-volume that can be controlled with closely observation through high-volume metastatic disease, which is lethal.

There are various risk factors involved in the initiation of this type of cancer such as: age, genetic factors, unhealthy diets, and so forth. The age is frequently correlated with this type of disease, which is proved by the fact that the development of prostate cancer increases with age.

Early low-grade prostate cancer does not present any signs or symptoms unless the metastatic spread occurs. The local growth can produce irrigative urinary symptoms and the spread can cause bone pain, but it can also appear in the forms of anorexia, fatigue, or weight loss.

There are many investigations used in the diagnosis of prostate cancer. Many of them are detected by the regular measurement of the prostate-specific antigen (also known as PSA), which is a glycoprotein made only by prostate cells. The increased total PSA and a small ratio of free PSA are frequently associated with the prostate malign neoplasm (Singer and DiPaola, 2013).

Other possible investigations to detect prostate cancer are biopsies, which can be transperineal template biopsies or MRI-targeted biopsies (magnetic resonance imaging), but the best results are obtained using the MRI-targeted method. If the results are positive for adenocarcinoma, the patients must do additional investigation and treatment. In this situation, an important role is provided by the MRI, which can offer information about the local extension of cancer. This information is very useful when radiotherapy or a radical prostatectomy is planned. If the MRI is not recommended for the patient, the CT scan can be used. In case of bone metastases, the whole-body bone scintigraphy is recommended, and also the PET method may be used to detect the metastases with the advantage that a diversity of radioactive tracers can be applied.

It is very important to understand the modifiable dietary and lifestyle factors that can initiate the prostate cancer progression and development. There is a research that upholds the ideas that prostate cancer prevention is possible by being physically active and a lifelong avoidance of obesity (Discacciati and Wolk, 2014).

One of the most common and aggressive forms of cancer both in children and in adults is leukemia. According to the World Health Organization, leukemia is in the top 15 common forms of malign neoplasm (Kampen, 2012). Leukemia is a malign neoplasm that begins in blood stem cells found in the bone marrow, a spongy and soft material that fills the center of bones.

Blood has three types of cells which are produced in the bone marrow: white blood cells that fight infections, red blood cells that carry oxygen and platelets that assist blood to clot. Normally, each day billions of blood cells are made in the bone marrow. As a rule, the red blood cells (erythrocytes) are the ones generated the most, but in the case of leukemia the human body begins to create more white cells than is necessary.

In this case, the leukemic cells are not able to fight infection, affect the normal functions of the vital organs, and the number of erythrocytes is decreased so the supply of oxygen is modified. Patients diagnosed with leukemia become anemic and present a high risk of infections and bleeding. At the moment, the conventional treatment is not efficient because it can cause side effects. The side effects are the result of the lack of specificity of the anticancer drugs because they do not only kill the cancer cells but also obstruct the development of normal cells, occasionally causing the necrosis of normal cells. One of the best ways to reduce drugs’ toxicity and to maintain its concentration for the needed period of time to direct the drug to its target site, so a lot of research has been done to develop smart drug delivery systems for leukemia treatment (Soni and Yadav, 2015).

3. Personalized Treatment of Cancer

Personalized oncology is focused on the use of personalized medicine in cancer treatment, considering the fact that tumor cells are various and multifaceted. The risk of a different response to a certain therapy may appear because tumors clinically look like a specific type but the difference can be observed only at a molecular level. For example, tumors can contain cancer stem cells that have different metastatic abilities and therapy responsiveness and most of them can be identified in breast, lung, and colon cancer. It is impractical to develop a general drug that can be applied to all patients with a certain disease because of the cancer heterogeneity. The solution would be to improve a treatment based on the characteristics of individual patients and diseases to match the requirement with the treatment (Liu, 2012).

To develop a personalized cancer treatment with new therapeutic agents, mechanisms such as cancer initiation and invasion must be analyzed at the molecular level. The multifunctionality of nanoparticles helps them incorporate biotargeting ligands such as antibodies, peptides, and small molecules or therapeutic drugs and transport them to the action site, as well as being useful in diagnosis and disease progress monitoring after chemotherapy. This technology facilitates early detection and a mixture of diagnostics with therapeutics. Personalized nanotechnology can also deliver cells or genes that are taken from the patient himself to improve the specific targeting of tumors and increasing the efficacy of treatment (Liu, 2012; Toy et al., 2014).

For personalized therapies there can be used individual biomarkers because they recognize the tumor tissue of the patient. These markers are difficult to find, which is why nanoparticles can be used to uncover the diagnostic and prognostic markers monitoring the efficacy of the treatment in a noninvasive way. For example, magnetic nanoparticles can catch circulating cancerous cells in bloodstream, quantum dots can notice the initial signs of cancer, and biosensors can find cancer biomarkers by discovering multiple protein markers in clinical samples (Liu, 2012).

3.1. Nanotechnology: Progress in Cancer Research

Nanotechnology refers to the development of structures and systems with the purpose to control their size and shape on a nanometer scale. A nanometer is considered the 10−9th part of a meter (Stylios et al., 2005). At this scale appears a good biological interaction between nanometric systems and natural structures, like proteins that are about 3–10 nm in size and blood cells that are approximately 6000 nm (Boisseau and Loubaton, 2011).

This type of technology has many applications in science, engineering, and especially medicine. Nanomedicine can be used for prevention, monitoring, diagnosis, control, and treatment, having an impact at the molecular level to achieve a medical benefit (Boisseau and Loubaton, 2011; Logothetidis, 2011; Stylios et al., 2005).

The diagnosis is the first step in a medical process and it can be made in vitro, through nanoparticles or nanodevices that recognize, capture, and concentrate natural biomolecules and also in vivo through synthetic assemblies that have the role of contrast agent for imaging. The imaging techniques that involve contrast agents are X-ray imaging, ultrasound imaging, and other diagnostic methods like magnetic resonance imaging, spectroscopy, or nuclear imaging (Boisseau and Loubaton, 2011; Toy et al., 2014).

The best diagnosis tool and image-guided therapy is the medical imaging as it helps in monitoring diseases and acting against them in vivo. A tissue disorder can be identified by a modification of its morphology or by using a contrast agent that assists in localizing a disease and obtaining a targeted treatment. This option helps in detecting the tumors’ localization and stage, inflammations, or drug accumulations that can be dangerous (De Souza et al., 2015).

Cancer cells can be detected through imaging after they cause a defect to a tissue that indicates that a great number of cells have grown and metastasized. Even if the tumor is detected, it is necessary to make a biopsy to establish the tumors’ nature (malignant or benign) and also determine the facts that can help the development of a treatment and make the tumor responsive to it. It is very important to identify the cancerous cell and to make it visible; through nanotechnologies these things can be achieved. Metal oxide nanoparticles provide a signal with a high contrast on the images of Magnetic Resonance or Computed Tomography and can be loaded with antibodies that recognize specific receptors on tumor cells (Boisseau and Loubaton, 2011).

Besides diagnostics and therapy, imaging can be useful also as an external stimulus for the activation of drug release from outside. The stimulus can be temperature, ultrasounds, or laser light. Biosensors have biological elements named enzymes that can recognize or signal the existence of a certain molecule and its activity. The biological signal is converted into a quantifiable signal through a transductor, to obtain a medical result (Boisseau and Loubaton, 2011).

Nanotechnology involves various devices, such as pills that can be swallowed for imaging or instruments for endoscopy to provide an accurate in vivo diagnostic. Implantable devices are used as well for glucose measurement or infection markers. As these devices are miniaturized, they are less invasive and can be better accepted by the body.

The diagnosis of brain cancer is very hard to obtain as a biopsy of the brain tissue because it is an invasive and dangerous technique. The alternative is a nanotechnology based on an endoscopic nanopatterned pen that can be used to collect cells and proteins by surface adhesion without affecting the brain tissue.

Nanotechnology can be used for the development of intelligent, biomimetic biomaterials that can cause positive reactions of cells and stimulate a specific regeneration process to create a new healthy tissue (Boisseau and Loubaton, 2011).

The possible applications of nanoscale technologies in the medical field are the following: controlled drug delivery systems for diagnosis and therapy, as they can provide a targeted delivery of active biological substances; cancer treatment by detecting and destroying the tumor; restoration of human organs and implants with higher biocompatibility (Logothetidis, 2011; Stylios et al., 2005). Nanotechnologies have applications in drug delivery systems and they refer to the dispersion of nanoobjects in the body, releasing active molecules in the biological fluids. The requirement of this type of nanotechnology is to combine the physicochemical characteristics of the delivery product with the biodistribution and pharmacokinetics of the active substance (Bazile, 2014).

The nanocarriers have specific characteristics such as nanometric size, favorable physical and chemical proprieties, and a high surface-to-volume ratio. They are useful by increasing drugs’ stability in the biological fluids, extending the blood circulation time, and releasing a controlled dilution of drugs (Wicki et al., 2015). Multifunctional nanocarriers aim not only to combine radiotherapy and chemotherapy, but also to accelerate the diagnostic process (Alexis et al., 2008).

As all the functions of the human body have daily variations and each organism has its own specific parameters, the normal drug administration does not always have a pharmacological effect. The best treatment should be closely connected to the biological pattern of each patient to deliver a certain drug at the right place, in the right moment, and with the right concentration. This idea can decrease the number of side effects of medical substances and minimize the medical crises (Stylios et al., 2005; Wicki et al., 2015).

A normal administration means that the drug will be delivered in the whole body and it will have in the first period an increased effect until a maximum level, decreasing after that and requiring a new administration. The main disadvantage is that healthy cells may be affected. With a targeted delivery, a long-term administration can be achieved for a specific organ with the necessary delivery rate and concentration. To carry the drugs, nanocarriers or drug delivery systems in form of nanoparticles, nanospheres, nanocapsules, or