Shape engineering boosts antibacterial activity of chitosan coated mesoporous silica nanoparticle doped with silver: a mechanistic investigation.

In this study, mesoporous silica nanoparticles (MSPs) of different size and shape were developed, and their surface coatings were utilized to study their differential effects in enhancing antibacterial activity. In brief, MSPs with three different aspect ratios (1, 2 and 4) were prepared, doped with silver ions and finally coated with the polymer chitosan. Both Gram-positive and Gram-negative bacteria were treated with the MSPs. Results indicate that silver ion doped and chitosan coated MSPs with the aspect ratio of 4 (Cht/MSP4:Ag+) have the highest antimicrobial activity among the prepared series. Further studies revealed that Cht/MSP4:Ag+ was most effective against Escherichia coli (E.coli) and least effective against Vibrio cholerae (V. cholerae). To investigate the detailed inhibition mechanism of the MSPs, the interaction of the nanoparticles with E.coli membranes and its intracellular DNA was assessed using various spectroscopic and imaging-based techniques. Furthermore, to increase the efficiency of the MSPs, a combinatorial antibacterial strategy was also explored, where nanoparticles, in combination with kanamycin (antibiotic), were used against Vibrio Cholerae (V. cholerae). Toxicity screening of these on MSPs was conducted on Caco-2 cells, and the results show that the dose used for antibacterial screening is below the limit of the toxicity threshold. Our findings show that both shape and surface engineering contribute positively towards killing bacteria, and the newly developed silver ion-doped and chitosan-coated MSPs have good potential as antimicrobial nanomaterials.

[1]  Yong-Kweon Kim,et al.  Surface-enhanced Raman scattering-active nanostructures and strategies for bioassays. , 2011, Nanomedicine.

[2]  J. Song,et al.  Does the Antibacterial Activity of Silver Nanoparticles Depend on the Shape of the Nanoparticle? A Study of the Gram-Negative Bacterium Escherichia coli , 2007, Applied and Environmental Microbiology.

[3]  A. Bakillah,et al.  Nutrition & Metabolism: an impressive performance since inception , 2013, Nutrition & Metabolism.

[4]  Jianlin Shi,et al.  Mesoporous silica nanoparticle based nano drug delivery systems: synthesis, controlled drug release and delivery, pharmacokinetics and biocompatibility , 2011 .

[5]  K. Pavelić,et al.  Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy , 2013, Nutrition & Metabolism.

[6]  H. Umezawa,et al.  Resistance mechanisms of kanamycin-, neomycin-, and streptomycin-producing streptomycetes to aminoglycoside antibiotics. , 1981, The Journal of antibiotics.

[7]  S. Faruque,et al.  Epidemiology, Genetics, and Ecology of ToxigenicVibrio cholerae , 1998, Microbiology and Molecular Biology Reviews.

[8]  S. Bhoraskar,et al.  Antimicrobial activity of silica coated silicon nano-tubes (SCSNT) and silica coated silicon nano-particles (SCSNP) synthesized by gas phase condensation , 2013, Journal of Materials Science: Materials in Medicine.

[9]  Thomas J Webster,et al.  Antimicrobial applications of nanotechnology: methods and literature , 2012, International journal of nanomedicine.

[10]  Albert Duschl,et al.  Hardening of the nanoparticle-protein corona in metal (Au, Ag) and oxide (Fe3O4, CoO, and CeO2) nanoparticles. , 2011, Small.

[11]  Frederico J. Gueiros-Filho,et al.  FtsZ filament capping by MciZ, a developmental regulator of bacterial division , 2015, Proceedings of the National Academy of Sciences.

[12]  Slobodan Ilic,et al.  Nutrition/Metabolism , 2011, Intensive Care Medicine.

[13]  O. Assis,et al.  A Review of the Antimicrobial Activity of Chitosan , 2009 .

[14]  N. Prabhakar,et al.  Design considerations for mesoporous silica nanoparticulate systems in facilitating biomedical applications , 2014 .

[15]  M. Odén,et al.  Tuning the shape of mesoporous silica particles by alterations in parameter space: from rods to platelets. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[16]  P. Chakrabarti,et al.  Bactericidal effect of polyethyleneimine capped ZnO nanoparticles on multiple antibiotic resistant bacteria harboring genes of high-pathogenicity island. , 2014, Colloids and surfaces. B, Biointerfaces.

[17]  Yumin Du,et al.  Chitosan- metal complexes as antimicrobial agent: Synthesis, characterization and Structure-activity study , 2005 .

[18]  U. Pal,et al.  Effects of crystallization and dopant concentration on the emission behavior of TiO2:Eu nanophosphors , 2012, Nanoscale Research Letters.

[19]  Adam J Friedman,et al.  Nanotechnology as a therapeutic tool to combat microbial resistance. , 2013, Advanced drug delivery reviews.

[20]  P. Stewart,et al.  Transmission Electron Microscopic Study of Antibiotic Action on Klebsiella pneumoniae Biofilm , 2002, Antimicrobial Agents and Chemotherapy.

[21]  Deborah Berhanu,et al.  The complexity of nanoparticle dissolution and its importance in nanotoxicological studies. , 2012, The Science of the total environment.

[22]  Ashutosh Kumar,et al.  Engineered ZnO and TiO(2) nanoparticles induce oxidative stress and DNA damage leading to reduced viability of Escherichia coli. , 2011, Free radical biology & medicine.

[23]  S. Mukherjee,et al.  CdO nanoparticle toxicity on growth, morphology, and cell division in Escherichia coli. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[24]  K. Jeyasubramanian,et al.  Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[25]  Chun-Ming Huang,et al.  Development of nanoparticles for antimicrobial drug delivery. , 2010, Current medicinal chemistry.

[26]  C. Hauser,et al.  In situ synthesis of size-controlled, stable silver nanoparticles within ultrashort peptide hydrogels and their anti-bacterial properties. , 2014, Biomaterials.

[27]  Y. Berger,et al.  The human intestinal epithelial cell line Caco-2; pharmacological and pharmacokinetic applications , 1995, Cell Biology and Toxicology.

[28]  Anders Baun,et al.  The challenges of testing metal and metal oxide nanoparticles in algal bioassays: titanium dioxide and gold nanoparticles as case studies , 2012, Nanotoxicology.

[29]  Kevin W Eliceiri,et al.  NIH Image to ImageJ: 25 years of image analysis , 2012, Nature Methods.

[30]  R. D'ari,et al.  Selected amplification of the cell division genes ftsQ-ftsA-ftsZ in Escherichia coli. , 2000, Genetics.

[31]  G. Alangaden,et al.  Mechanism of Resistance to Amikacin and Kanamycin in Mycobacterium tuberculosis , 1998, Antimicrobial Agents and Chemotherapy.

[32]  K. Ahmed,et al.  Copper nanoparticles as an efflux pump inhibitor to tackle drug resistant bacteria , 2015 .

[33]  P. Ducheyne,et al.  Polymer-coated mesoporous silica nanoparticles for the controlled release of macromolecules. , 2012, Acta biomaterialia.

[34]  J. Trevors,et al.  Cytoplasmic membrane polarization in Gram-positive and Gram-negative bacteria grown in the absence and presence of tetracycline. , 2004, Biochimica et biophysica acta.

[35]  M. B. Cardoso,et al.  Tailored silica-antibiotic nanoparticles: overcoming bacterial resistance with low cytotoxicity. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[36]  J. M. Córdoba,et al.  Rapid synthesis of SBA-15 rods with variable lengths, widths, and tunable large pores. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[37]  H. Gu,et al.  Modulation of the structural properties of mesoporous silica nanoparticles to enhance the T1-weighted MR imaging capability. , 2016, Journal of materials chemistry. B.

[38]  Juan L. Vivero-Escoto,et al.  Mesoporous silica nanoparticles for reducing hemolytic activity towards mammalian red blood cells. , 2009, Small.

[39]  Erik N. Taylor,et al.  Reducing infections through nanotechnology and nanoparticles , 2011, International journal of nanomedicine.

[40]  Muhammad Ilyas,et al.  Impact of nanoparticles on human and environment: review of toxicity factors, exposures, control strategies, and future prospects , 2015, Environmental Science and Pollution Research.

[41]  J. Jang,et al.  Enhanced antibacterial activity of silver/polyrhodanine-composite-decorated silica nanoparticles. , 2013, ACS applied materials & interfaces.

[42]  P. Chakrabarti,et al.  The Molecular Basis of Inactivation of Metronidazole-Resistant Helicobacter pylori Using Polyethyleneimine Functionalized Zinc Oxide Nanoparticles , 2013, PloS one.

[43]  H. Sahl,et al.  Insights into the Mode of Action of Chitosan as an Antibacterial Compound , 2008, Applied and Environmental Microbiology.

[44]  I. Sondi,et al.  Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. , 2004, Journal of colloid and interface science.

[45]  Bengt Fadeel,et al.  Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release , 2014, Particle and Fibre Toxicology.

[46]  P. Eklund,et al.  Rational evaluation of the utilization of PEG-PEI copolymers for the facilitation of silica nanoparticulate systems in biomedical applications. , 2014, Journal of colloid and interface science.

[47]  J. Costerton,et al.  Evaluation of Fleroxacin Activity against Established Pseudomonas fluorescens Biofilms , 1994, Applied and environmental microbiology.

[48]  Z. Guan,et al.  The Outer Surface Lipoprotein VolA Mediates Utilization of Exogenous Lipids by Vibrio cholerae , 2013, mBio.

[49]  P. Chakrabarti,et al.  The antimicrobial activity of ZnO nanoparticles against Vibrio cholerae: Variation in response depends on biotype. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[50]  Linlin Li,et al.  Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery , 2012, Advanced materials.

[51]  J. Zink,et al.  Antimicrobial Activity of Silver Nanocrystals Encapsulated in Mesoporous Silica Nanoparticles , 2009 .

[52]  Wojciech Zareba,et al.  Ambient fine particulate air pollution triggers ST-elevation myocardial infarction, but not non-ST elevation myocardial infarction: a case-crossover study , 2014, Particle and Fibre Toxicology.

[53]  H. Sahl,et al.  Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ , 2011, Proceedings of the National Academy of Sciences.

[54]  J. Collins,et al.  Dinuclear ruthenium(II) antimicrobial agents that selectively target polysomes in vivo , 2014 .

[55]  Y. Hwang,et al.  Photoluminescence characteristics of Cd1-xMnxTe single crystals grown by the vertical Bridgman method , 2012, Nanoscale Research Letters.

[56]  Mark A. Miller,et al.  Enteric infections, diarrhea, and their impact on function and development. , 2008, The Journal of clinical investigation.

[57]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[58]  D. Scherman,et al.  Mesoporous persistent nanophosphors for in vivo optical bioimaging and drug-delivery. , 2014, Nanoscale.

[59]  R. Iler The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties and Biochemistry of Silica , 1979 .

[60]  Didem Şen Karaman,et al.  Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect. , 2015, Biomaterials science.

[61]  Ruchira Chakraborty,et al.  A simple robust method for synthesis of metallic copper nanoparticles of high antibacterial potency against E. coli , 2012, Nanotechnology.

[62]  ScienceDirect Nanomedicine : nanotechnology, biology and medicine. , 2005 .

[63]  Young Jik Kwon,et al.  "Nanoantibiotics": a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[64]  F. Corona,et al.  The intrinsic resistome of bacterial pathogens , 2013, Front. Microbiol..

[65]  W. D. de Jong,et al.  Drug delivery and nanoparticles: Applications and hazards , 2008, International journal of nanomedicine.

[66]  Sanath H. Kumar,et al.  Potential for inhibition of bacterial efflux pumps in multidrug-resistant Vibrio cholera , 2013, The Indian journal of medical research.

[67]  H. Santos,et al.  Mesoporous Biomaterials – multifunctional materials for future medical therapies and bioanalysis , 2015 .

[68]  L. Rice The clinical consequences of antimicrobial resistance. , 2009, Current opinion in microbiology.