J Nanopart Res (2015)17:201

DOI 10.1007/s11051-015-3004-7

RESEARCH PAPER

Nanostructured mesoporous silica: new perspectives

for fighting antimicrobial resistance
Georgeta Voicu . Ionu Dogaru . Daniela Meli . Raluca Meterc .
Vera Spirescu . Eliza Stan . Eliza Tote . Laureniu Mogoant .
George Dan Mogoanu . Alexandru Mihai Grumezescu . Roxana Truc .
Eugeniu Vasile . Florin Iordache . Mariana-Carmen Chiriuc . Alina Maria Holban

Received: 3 April 2014 / Accepted: 13 April 2015

Springer Science+Business Media Dordrecht 2015

Abstract This paper investigates the antimicrobial

potential of nanostructured mesoporous silica (NMS)
functionalized with essential oils (EOs) and antibiotics
(ATBs). The NMS networks were obtained by the
basic procedure from cetyltrimethylammonium bromide and tetraethyl orthosilicate in the form of
granules with diameters ranging from 100 to 300 nm
with an average pore diameter of 2.2 nm, as confirmed
by the BETTEM analyses. The Salvia ofcinalis (SO)
and Coriandrum sativum (CS) EOs and the streptomycin and neomycin ATBs were loaded in the NMS

pores. TG analysis was performed in order to estimate

the amount of the entrapped volatile EOs. The results
of the biological analyses revealed that NMS/SO and
NMS/CS exhibited a very good antimicrobial activity
to an extent comparable or even superior to the one
triggered by ATB, and a good in vitro and in vivo
biocompatibility. Due to their regular pores, high
biocompatibility, antimicrobial activity, and capacity
to stabilize the volatile EOs, the obtained NMS can be
used as an efficient drug delivery system for further
biomedical applications.

G. Voicu I. Dogaru D. Melita

R. Mesterca V. Spirescu E. Stan E. Tote
A. M. Grumezescu (&) E. Vasile A. M. Holban
Department of Science and Engineering of Oxide
Materials and Nanomaterials, Faculty of Applied
Chemistry and Materials Science, Politehnica University
of Bucharest, Polizu Street No 1-7, 011061 Bucharest,
Romania
e-mail: grumezescu@yahoo.com

G. D. Mogosanu
Department of Pharmacognosy & Phytotherapy, Faculty
of Pharmacy, University of Medicine and Pharmacy of
Craiova, 2 Petru Rares Street, 200349 Craiova, Romania

I. Dogaru D. Melita R. Mesterca V. Spirescu

E. Stan E. Tote A. M. Grumezescu
Department of Biomaterials and Medical Devices, Faculty
of Medical Engineering, University Politehnica of
Bucharest, Polizu Street, No 1-7, 011061 Bucharest,
Romania
L. Mogoanta
Research Center for Microscopic Morphology and
Immunology, University of Medicine and Pharmacy of
Craiova, 2 Petru Rares Street, 200349 Craiova, Romania

R. Trusca
Metav SA-CD S.A., 31 Rosetti Street, 020015 Bucharest,
Romania
F. Iordache
Department of Fetal and Adult Stem Cell Therapy,
Institute of Cellular Biology and Pathology of Romanian
Academy, Nicolae Simionescu, 8, B.P. Hasdeu, 050568
Bucharest, Romania
M.-C. Chifiriuc A. M. Holban
Microbiology Department, Faculty of Biology, University
of Bucharest, Aleea Portocalelor No 1-3, 060101
Bucharest, Romania

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Keywords Nanostructured mesoporous silica

Biocompatibility S. aureus P. aeruginosa
Essential oils Drug delivery

Introduction
Staphylococcus aureus is the most versatile and well
studied Gram-positive bacteria, causing severe infections in hospitalized patients, especially in intensive
care units and in patients bearing prosthetic devices
(Yan et al. 2013; Holban et al. 2013). S. aureus also
exhibits high resistance to many physical, chemical,
and biological agents (Yan et al. 2013; Holban et al.
2013). Methicillin-resistant S. aureus strains are resistant not only to penicillins and cephalosporins, but also
to other classes of anti-staphylococcal antibiotics
(fluoroquinolones, aminoglycosides), being responsible for staphylococcal infections with severe evolution
and high mortality rates (Tacconelli et al. 2008).
On the other hand, the opportunistic pathogen
Pseudomonas aeruginosa is one of the most lifethreatening Gram-negative bacteria, particularly in
immunocompromised and cystic fibrosis patients
(Holban et al. 2013). P. aeruginosa can easily adapt
to any environment, mainly due to its ability to form
biofilms on different industrial equipments and
medical surfaces, causing major health-related and
economical issues (Kim et al. 2013). P. aeruginosa is
naturally resistant to the majority of currently used
drugs and may also acquire resistance during or after
antibiotic treatment (Poole 2004).
In the recent years, finding new or alternative
treatments to cure dangerous, drug-resistant infections,
became one of the top priorities of the biomedical
research (Tacconelli et al. 2008). Developing antimicrobial therapies based on natural compounds
represents a desirable strategy to fight resistant infections, to decrease the rate of selecting resistant mutants
and also to reduce the side effects associated with the
use of synthetic drugs (Saviuc et al. 2013; Grumezescu
2013; Grumezescu et al. 2012; Chifiriuc et al. 2012;
Grumezescu et al. 2012; Saviuc et al. 2012; Anghel
et al. 2013; Anghel et al. 2013; Istrate et al. 2014).

J Nanopart Res (2015)17:201

Ecological therapies based on natural products are

the most investigated nowadays. Studies revealed that
some plant-related products and essential oils (EOs)
may have a very good antimicrobial activity. As for
example Salvia ofcinalis (SO) has attracted the
attention of researchers in recent years due to its high
content of different biological active compound as
essential oil and antioxidant compounds. Essential oil
of S. ofcinalis is proved to be effective against many
pathogens as Bacillus subtilis, S. aureus, P. aeruginosa,
Escherichia coli, Candida albicans, and Aspergillus
niger (Miladinovi and Miladinovic 2012). Coriander
Coriandrum sativum (CS) proved to have also a great
antimicrobial effect against E. coli, B. subtilis, and
Saccharomyces cerevisiae (Cao et al. 2012).
Silica networks (fibers, spheres, core/shell, magnetic
hollow silica, or silica nanocomposites) have attracted
much attention in the last years due to their large specific
surface areas, very well-defined and uniform porosity,
inert framework, and good biocompatibility (Xu et al.
2013; Bariana et al. 2013; Chen et al. 2013; Benhamou
et al. 2013; Qiang et al. 2013; Roik and Belyakova 2013;
Voicu et al. 2014), as well as to their capability to improve
the antimicrobial effect and to deliver different therapeutic
agents (Grumezescu et al. 2013; Berlier et al. 2013; Voicu
et al. 2013; Mihaiescu et al. 2013; Balaure et al. 2013;
Grumezescu et al. 2013; Arean et al. 2013). Recent studies
reported that silica networks may be used as efficient
shuttles for improving the efficiency of several ATB drugs
such as aminoglycosides, polymyxin, norfloxacin, and
cefotaxime (Anghel et al. 2012, 2014). Although their
enhancing effect on the activity of synthetic drugs has
been proved, current literature offers very few data
regarding their ability to stabilize and control the release of
natural products and compounds (Kaya et al. 2013).
The aim of this study was to prepare, characterize,
and evaluate some of their biological activities, i.e.,
(i) biocompatibility, (ii) the potential of mesoporous
silica networks to stabilize and control the release of
EOs, and (iii) to improve the activity of current ATBs.

Materials and methods

Materials

M.-C. Chifiriuc
Life, Environment and Earth Sciences Section, Research
Institute of the University of Bucharest-ICUB, Spl.
Independentei 91-95, Bucharest, Romania

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Cetyltrimethylammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), ammonium hydroxide

(NH4OH), ATB streptomycin (STR), and neomycin

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(NEO) were purchased from Sigma-Aldrich. SO and

CS were purchased from a local supplier. All
chemicals were of analytical purity and used with
no further purification.
Preparation of nanostructured mesoporous silica
(NMS)
NMS were prepared according to Kalbasi and
Mosaddegh (2011). Briefly, the CTAB (2.4 g) was
dissolved in 50 mL deionized water. Thereafter,
44 mL of ethanol and 16 mL of NH4OH (25 %) were
added and the mixture was stirred for 10 min.
Subsequently, 3.4 g of TEOS was added and the
mixture was incubated at room temperature for 4 h.
The resulting powder was filtered, washed with
deionized water, and dried. The templating agent
CTAB was removed by calcination, at 650 C for 6 h.

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USA). The microscope was operated in transmission

mode at 300 kV with TEM point resolution of 2 A

. The prepared powder was
and line resolution of 1 A
dispersed into pure ethanol and ultrasonicated for
15 min. Thereafter, the diluted sample was poured
onto a holey carbon-coated copper grid and left to dry
before TEM analysis.
BET
The BrunauerEmmettTeller (BET) analysis was
performed on a Micrometrics Gemini V2 model
2380-surface area and pore size analyzer. The
adsorption isotherms were obtained by measuring
the amount of gas adsorbed across a wide range of
relative pressures at a constant temperature (N2, 77 K,
and pressure between 780 and 7.8 mmHg). Conversely, desorption isotherms were achieved by
measuring the gas removed as pressure was reduced.

Preparation of NMS/EOs and NMS/ATB

XRD
The ATBs were entrapped into the NMS at a final
concentration of 20 %, i.e., 100 mg of NMS/ATB
containing 80 mg NMS and 20 mg ATB. The NMS
and the antibiotics (STR, NEO) to be entrapped were
mixed in the presence of 1 mL of ultrapure water
until the latter completely evaporated at 40 C.
In the case of EOs, due to their volatility, the NMS
(100 mg) and the EOs (SO, CS) (100 L) to be
entrapped were mixed and kept at room temperature
for 7 days. After 7 days, the content of EOs onto
NMS/SO and NMS/CS was estimated by thermogravimetric analysis (TG).
Characterization
SEM
SEM analysis was performed on a FEI electron
microscope, using secondary electron beams with
energies of 30 keV, on samples covered with a thin
gold layer.
TEM
The transmission electron microscopy (TEM) images
were obtained on finely powdered samples using a
TecnaiTM G2 F30 S-TWIN high resolution transmission electron microscope from FEI Company (OR,

X-ray diffraction analysis was performed on a

Shimadzu XRD 6000 diffractometer at room temperature. In all cases, Cu K radiation from a Cu
X-ray tube (run at 15 mA and 30 kV) was used. The
samples were scanned in the Bragg angle 2 range of
1080 degree.
TG analysis
The TG analysis of the NMS, NMS/SO, and NMS/CS
was performed with a Shimadzu DTG-TA-50H
instrument. Samples were screened to 200 mesh prior
to analysis, placed in alumina crucible, and heated
with 10 K min1 from room temperature to 800 C,
under a flow of 20 mL min1 dried synthetic air (80 %
N2 and 20 % O2).
Infrared (IR) mapping
IR mapping was recorded on a Nicolet iN10 MX FTIR Microscope with MCT liquid nitrogen cooled
detector in the measurement range of 4000700 cm1.
Spectral collection was performed in reflection mode
at 4 cm1 resolution. For each spectrum, 32 scans
were co-added and converted to absorbance using
OmnicPicta software (Thermo Scientific). Approximately, 400 spectra were analyzed for each

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sample. Two absorption peaks known as being

characteristics for the NMS and for the therapeutic
agents were selected as spectral markers.
Cytotoxicity assay
Human endothelial cells (EAhy926 cell line, ATCC,
USA) were grown in DMEM culture medium containing 10 % fetal bovine serum (FBS), and 1 %
penicillin and NEO (Sigma-Aldrich, St. Louis, MO,
USA). For cell proliferation and viability, the
CellTiter96 Non-Radioactive Cell Proliferation Assay (Promega, Madison, USA) was used. Endothelial
cells were seeded in a 96-well plate at a density of
5 9 103 cells/well, in DMEM medium, supplemented
with 10 % FBS, and incubated with the NMS
materials (added to a final concentration of 1 mg/
mL) for 72 h, while the controls were represented by
endothelial cells grown in the same culture conditions, but on bare substrates. Cell proliferation assay
was performed in triplicates, according to manufacturers guidelines, at different time intervals. Briefly,
15 L of Promega Kit Solution I were added in each
well and incubated for 4 h. Furthermore, 100 L of
Promega Kit Solution II were added in the 96-well
plate and incubated for 1 h followed by spectrophotometry measurements performed at 570 nm, using a
Mithras LB 940 spectrophotometer (Berthold Technology, Germany) (Grumezescu et al. 2014).
The RED CMTPX fluorophore (Life Technologies, Invitrogen, USA), a long-term living cells
tracker was added in the culture medium at a final
concentration of 5 M, incubated for 30 min to allow
the dye to penetrate through the cells. Furthermore,
the cells were washed with phosphate-buffered saline
(PBS) and visualized by fluorescence microscopy.
The nuclei were counterstained with DAPI (1 mg/
mL). Living cells tracing in the presence of nanospheres was monitored for 5 days in culture. The
micrographs were taken by a digital camera driven by
the Axio-Vision 4.6 (Carl Zeiss, Germany) software
Kaya et al. 2013).
Histological analysis
The experimental protocol was applied according to
the European Council Directive No. 86/609/November 24, 1986, the European Convention on the
Protection of Vertebrate Animals (2005), and the

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Romanian Government Ordinance No. 37/February

2, 2002.
For histological analysis, two groups of mice (of 6
mice each) were used for the NMS sample and for
reference. The mice were intraperitoneally inoculated
in the groin area, with 200 L of 1 mg/mL NMS
suspension prepared in ultrapure water. The NMS
powder was previously sterilized by UV irradiation
for 30 min. The reference mice were inoculated with
200 L of ultrapure water. At 7 days and 14 days
after inoculation, the animals were euthanized, under
general anesthesia, for the sampling of internal
organs (brain, liver, myocardium, pancreas, lung,
kidney, spleen). Immediately after sampling, the
biological material was washed in PBS to remove
blood. Then, the internal organs were fixed in 10 %
buffered neutral formalin, for 72 h, at room temperature and processed by paraffin embedding
technique for routine histological analysis. In this
purpose, 4-m thick serial sections were cut on a
MICROM HM355 s rotary microtome (MICROM
International GmbH, Walldorf, Germany) equipped
with a waterfall-based section transfer system (STS,
MICROM). The cross sections were placed on
histological blades treated with poly-L-Lysine (Sigma-Aldrich, Munich, Germany). After Hematoxylin
Eosin (HE) classic staining, cross sections were
evaluated and photographed using a Nikon Eclipse
55i light microscope equipped with a Nikon DSFi1
CCD high definition video camera (Nikon Instruments, Apidrag, Romania). Images were captured,
stored, and analyzed using the Image ProPlus 7 AMS
software (Media Cybernetics Inc., Marlow, Buckinghamshire, UK) (Holban et al. 2014; Mogosanu et al.
2013).
Antimicrobial activity testing
Staphylococcus aureus ATCC 25923 and P. aeruginosa ATCC 27853 (ATCC, US) strains were used in
this study. Quantitative testing of the antimicrobial
activity of NMS/STR, NMS/NEO, NMS/EOs was
performed by microdilution technique in liquid
medium (MuellerHinton broth), using 96 multi-well
plates in order to establish the minimum inhibitory
concentration (MIC; Bariana et al. 2013). Twofold
serial microdilutions were achieved in 200 L medium, the dilution range varying, depending on the
tested antibiotic and the bacterial strain, in

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accordance with the CLSI breakpoints. Subsequently,

the wells were seeded with 50 L of each bacterial
suspension, adjusted to 0.5 MacFarland density (1
3 9 108 CFU/mL). Positive (microbial cultures
grown in the absence of NMS suspensions) and
negative controls (sterile culture medium) were used.
After incubating the plates at 37 C for 24 h, the
results were macroscopically assessed for bacterial
growth, the MIC value corresponding to the last well
with clear content, thus without no visible microbial
growth. Experiments were performed in triplicate and
repeated on at least three different occasions.
Statistics
Results have been statistically analyzed using one
way ANOVA test with Graph Pad Prism v5 software.
p values lower than 0.05 were considered significant.

Results and discussion

The morphology of the NMS network calcinated at
650 C for 6 h was studied by SEM and TEM. The
SEM images of the prepared silica structure are
shown in (Fig. 1a, b), revealing a spherical morphology of the NMS sample, with sizes ranging from
100 to 400 nm. The TEM images shown in (Fig. 1c,
d) indicate a pore size diameter of the prepared NMS
of around 2.2 nm. These results are in agreement with
the BET analysis.
The NMS network was further characterized by N2
adsorptiondesorption isotherm (Fig. 2a), where a
typical type I curve was observed, indicating the
mesoporous structure of the prepared NMS (Li et al.
2013). The BET surface area of NMS was of
1002.9 m2/g and the Langmuir surface area of
1498.1 m2/g. The corresponding average pore size
diameter, calculated from the desorption curve using
BarrettJoynerHalenda was of 2.2 nm.
The XRD pattern of the NMS presented in Fig. 2b
shows a broad peak in the range of 1535 (2),
suggesting an amorphous structure.
Figure 2c presents the TGA curves of the NMS,
NMS/SO, and NMS/CS, describing the variation of
mass loss according to temperature. It can be
observed that the amount of SO entrapped onto
NMS/SO was about 19.60 % and that of CS to be

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about 34 %. These data will further be used in the

biological assays.
Figure 3 presents the IR mapping and spectra of
NMS/NEO (a), NMS/STR (b), NMS/CO (c), and
NMS/SO (d). Similar to the NMS matrix, NMS/EOs,
and NMS/ATB show the typical vibrations of asymmetric and symmetric stretching, as well as the
rocking of SiOSi at ~12601270 and 980 cm1.
The presence of the ATB is proved by the absorption
bands characteristic to C=O or C=O(OH) groups
present in both ATB. In the IR spectra, the C=O
group assigned to STR and NEO appears at around
1676 cm1 and at 1631 cm1, respectively. The
presence of EOs was proved by the presence of the
absorption bands characteristic to C=O and CH
aliphatic and aromatic groups. Also, Fig. 5 presents
the distribution and relative density of the above
characteristic functional groups on the surface of the
prepared silica materials. This analysis thus confirms
that the ATB and EOs are present in the prepared
NMS materials (Grumezescu et al. 2013).
Recent studies reveal that silica may have a
cytotoxic activity, depending on their type, target
cells, and synthesis method (Hudson et al. 2008). Our
in vitro MTT assay results revealed that the fabricated bio-active NMS network has a good
biocompatibility, without any significant effect on
the normal metabolism and development of humancultured endothelial cells, at 24 and 48 h (Fig. 4). An
enhanced cellular metabolism and growth was observed in the presence of NMS structures after 72 h of
incubation, but these results could be due to the fact
that longer incubation time results in the accumulation of color and increased sensitivity of the method
(Riss et al. 2013).
Giving that incubation of the tetrazolium reagents
with viable cells increases the possibility of artifacts
resulting from chemical interactions among the assay
chemistry, the compounds being tested, and the
biochemistry of the cell, the use of a second method
to assess cytotoxicity is recommended. In our study,
we have used fluorescence microscopy to evaluate the
effect of the fabricated NMS upon the mammalian
cells. The fluorescence microscopy images showed
that human endothelial cells have a normal morphology, adherence, and distribution when growing
in the presence of the tested NMS (Fig. 5). These
observations support the fact that the fabricated

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Fig. 1 SEM (a, b) and TEM (c, d) images of NMS

materials may be safely used for further biomedical

applications.
The in vivo assay based on the histological
examination of the vital organs of balbC mice
inoculated intraperitoneally with the obtained NMS
demonstrated that the nanoparticles are absent in most
vital organs, excepting the spleen, suggesting that they
can be transported through the blood vessels and may
cluster in highly blood-irrigated organs, as the spleen,

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but no pathological modifications were observed in any

of the analyzed organs (Figs. 6, 7, 8).
Despite their insignificant effect on human and mice
cells, the functionalized materials (NMS/EOs and NMS/
ATB) proved a great inhibitory activity on bacterial cells.
Their antimicrobial activity was tested against Grampositive (S. aureus) and Gram-negative (P. aeruginosa)
bacterial strains, frequently encountered in nosocomial
infections and exhibiting high antibiotic resistance rates.

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Fig. 2 a N2 adsorptiondesorption isotherm of prepared NMS, b XRD pattern of NMS, c TG analysis of NMS, NMS/SO, and NMS/
CS

Antimicrobial activity of the NMS loaded

with essential oils
In the case of EOs containing materials, both NMS/
SO and NMS/CS exhibited a high-antimicrobial
effect against S. aureus and P. aeruginosa strains.
NMS/SO proved a higher microbicidal impact when
used in low concentrations than NMS/CS (Fig. 8).
Previous studies proved the ability of natural and
synthetic silica networks to potentiate the activity of
several ATB against microbial species, but to our
knowledge this is one of the first studies reporting the
ability of silica nanomaterials to stabilize the antimicrobial activity of natural products, as EOs.

Moreover, NMS/EOs proved an antimicrobial effect

comparable to that of ATB against S. aureus. Thus,
when used in amounts of 7.81 g/mL, 3.90 g/mL,
and even 1.95 g/mL, the NMS/SO and NMS/CS
bio-active nanostructured silica reduced the viability
of bacteria with an efficiency of at least 20 % higher
as compared with the plain STR control (Fig. 9a).
Antimicrobial activity of the NMS loaded
with antibiotics
The antimicrobial assay revealed that NMS improved
the activity of the tested ATB. NMS/STR bio-active
nanomaterial proved a much intensive antimicrobial

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b Fig. 3 Second derivate IR mapping (1,2) and spectra (3) of

NMS/NEO (a), NMS/STR (b), NMS/CO (c), NMS/SO (d):

intensity distribution of SiOSi (1) and C=O (2)

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with the same amount of STR, which reduced the

bacterial viability with less than 50 %. Furthermore,
this difference can be observed also at lower
concentrations, respectively, at 1.95 and 0.97 g/
mL. The NMS was also efficient in improving the
antimicrobial effect of NEO against P. aeruginosa
strain, an amount of 1.95 g/mL reducing the
bacterial viability with 77 %, while the same amount
of plain antibiotic NEO only by 40 % (Fig. 9b).

Conclusions

Fig. 4 Graphic representation of the MTT results obtained by

analyzing endothelial cells grown in the presence of tested bioactive nanostructured silica for 24, 48, and 72 h. *p \ 0.05
(labeled samples vs. control on the same time point); one way
ANOVA test

effect as compared with the plain antibiotic control

STR. The data demonstrate that an amount of
3.90 g/mL MCM-48/STR decreased the viability
of S. aureus cells with more than 70 %, comparing

The present study shows the synthesis of NMS

particles, with highly regular pores of an average
diameter of 2.2 nm. The silica networks loaded with
synthetic antimicrobial agents significantly reduced
the MIC as compared to the plain therapeutic agents.
Moreover, the silica networks loaded with EOs
proved an antimicrobial activity superior to that of
the NMS loaded with ATB. Their good biocompatibility and the fact that they may be used as
stabilizers for different natural compounds with
antimicrobial effect recommend the fabricated materials as competitive nominees for the development of
novel strategies for fighting resistant infections.

Fig. 5 Fluorescence microscopy images of viable endothelial cells stained with RED CMTPX fluorophore, grown in the presence of
tested bio-active NMS (concentration of 1 mg/mL) versus control (endothelial cells grown in standard conditions)

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Fig. 6 Transversal sections through the mice internal organs,

treated with NMS for 7 days. No NMS were detected. The
analyzed organ samples proved a normal aspect. HE staining:

a brain, 9200; b liver, 9200; c myocardium, 9400; d pancreas,

9200; e lung, 9200; f kidney, 9400

Fig. 7 Transversal sections through the mice internal organs,

treated with NMS for 14 days. No NMS were detected. The
analyzed organ samples proved a normal aspect. HE staining:

a brain, 9200; b liver, 9200; c myocardium, 9400; d pancreas,

9200; e lung, 9400; f kidney, 9400

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Fig. 8 Transversal sections through the mice spleen (9400),

treated with NMS for 7 days (a) and 14 days (b). NMS were
observed in large amounts only into the red pulp of the spleen
after 14 days, compared with the sample collected at 7 days;

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Transversal sections through the mice spleen untreated for

7 days (c) and 14 days (d). Nanostructures are missing. Normal
histological aspects are observed

Fig. 9 Graphic
representation of the effect
of different concentrations
of NMS/SO, NMS/CS,
NMS/STR, and NMS/NEO
on the viability of S. aureus
(a) and P. aeruginosa
(b) tested strains

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Acknowledgments This research was financially supported

by Sectoral Operational Programme Human Resources
Development, financed from the European Social Fund and by
the Romanian Government under the contract number POSDRU/
156/1.2/G/135764. Improvement and implementation of
university master programs in the field of Applied Chemistry
and Materials Science-ChimMaster.

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