Nano-vehicles give new lease of life to existing antimicrobials

Antibiotic resistance has become one of the greatest challenges for modern medicine, and new approaches for the treatment of bacterial infections are urgently needed to avoid widespread vulnerability again to infections that have so far been easily treatable with existing drugs. Among the many approaches investigated to overcome this challenge is the use of engineered nanostructures for the precise and targeted delivery of existing antimicrobial agents in a fashion that will potentiate their effect. This idea leans on lessons learned from pioneering research in cancer, where the targeted delivery of anti-cancer drugs to mammalian cells has been a topic for some time. In particular, new research has demonstrated that nanomaterials can be functionalised with active antimicrobials and, in some cases, with targeting molecules that potentiate the efficiency of the antimicrobials. In this mini-review, we summarise results that demonstrate the potential for nanoparticles, dendrimers and DNA nanostructures for use in antimicrobial delivery. We consider material aspects of the delivery vehicles and ways in which they can be functionalised with antibiotics and antimicrobial peptides, and we review evidence for their efficacy to kill bacteria both in vitro and in vivo. We also discuss the advantages and limitations of these materials and highlight the benefits of DNA nanostructures specifically for their versatile potential in the present context.

[1]  Maria Luisa Mangoni,et al.  Gold-nanoparticles coated with the antimicrobial peptide esculentin-1a(1-21)NH2 as a reliable strategy for antipseudomonal drugs. , 2017, Acta biomaterialia.

[2]  Yanmei Shi,et al.  Multivalent and synergistic chitosan oligosaccharide-Ag nanocomposites for therapy of bacterial infection , 2020, Scientific Reports.

[3]  C. Kaminski,et al.  DNA Nanostructures for Targeted Antimicrobial Delivery , 2020, Angewandte Chemie.

[4]  T. Xu,et al.  Polyamidoamine (PAMAM) dendrimers as biocompatible carriers of quinolone antimicrobials: an in vitro study. , 2007, European journal of medicinal chemistry.

[5]  R. Cavalli,et al.  Nanoparticulate Delivery Systems for Antiviral Drugs , 2010, Antiviral chemistry & chemotherapy.

[6]  S. Prabhu,et al.  Silver nanoparticles: mechanism of antimicrobial action, synthesis, medical applications, and toxicity effects , 2012, International Nano Letters.

[7]  Weihong Tan,et al.  Nanotechnology in therapeutics : a focus on nanoparticles as a drug delivery system Review , 2008 .

[8]  M. Khrestchatisky,et al.  Synthetic therapeutic peptides: science and market. , 2010, Drug discovery today.

[9]  R. Haag,et al.  Mannose-Functionalized Hyperbranched Polyglycerol Loaded with Zinc Porphyrin: Investigation of the Multivalency Effect in Antibacterial Photodynamic Therapy. , 2017, Chemistry.

[10]  Hao Wang,et al.  Enzyme‐Coated Mesoporous Silica Nanoparticles as Efficient Antibacterial Agents In Vivo , 2013, Advanced healthcare materials.

[11]  Nastassja A. Lewinski,et al.  Cytotoxicity of nanoparticles. , 2008, Small.

[12]  J. Majoral,et al.  Synergistic Effects of Anionic/Cationic Dendrimers and Levofloxacin on Antibacterial Activities , 2019, Molecules.

[13]  Anirban Bhunia,et al.  A Peptide-Nanoparticle System with Improved Efficacy against Multidrug Resistant Bacteria , 2019, Scientific Reports.

[14]  Tomoko Emura,et al.  A Photocaged DNA Nanocapsule for Controlled Unlocking and Opening inside the Cell. , 2019, Bioconjugate chemistry.

[15]  P. Ortega,et al.  Nanosystems as Vehicles for the Delivery of Antimicrobial Peptides (AMPs) , 2019, Pharmaceutics.

[16]  H. Dinh,et al.  Reaction of ribulose biphosphate carboxylase/oxygenase assembled on a DNA scaffold. , 2019, Bioorganic & medicinal chemistry.

[17]  P. Rothemund.  Folding DNA to create nanoscale shapes and patterns , 2006, Nature.

[18]  Yue Zhang,et al.  Nanoparticle-based local antimicrobial drug delivery. , 2017, Advanced drug delivery reviews.

[19]  P. Pendleton,et al.  Mesoporous silica as a natural antimicrobial carrier , 2011 .

[20]  C. Toniolo,et al.  Peptides on the Surface: Spin-Label EPR and PELDOR Study of Adsorption of the Antimicrobial Peptides Trichogin GA IV and Ampullosporin A on the Silica Nanoparticles , 2016 .

[21]  J. Lazniewska,et al.  Cytotoxicity of Dendrimers , 2019, Biomolecules.

[22]  M. Sardar,et al.  Ampicillin Silver Nanoformulations against Multidrug resistant bacteria , 2019, Scientific Reports.

[23]  E. Ruoslahti,et al.  Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy , 2018, Nature Biomedical Engineering.

[24]  K. Rumbaugh,et al.  One-step synthesis of high-density peptide-conjugated gold nanoparticles with antimicrobial efficacy in a systemic infection model. , 2016, Biomaterials.

[25]  Dongqiang Zhu,et al.  Adsorption of pharmaceutical antibiotics on template-synthesized ordered micro- and mesoporous carbons. , 2010, Environmental science & technology.

[26]  G. Armstrong,et al.  In vivo supramolecular templating enhances the activity of multivalent ligands: A potential therapeutic against the Escherichia coli O157 AB5 toxins , 2008, Proceedings of the National Academy of Sciences.

[27]  Quansheng Chen,et al.  Enhancing the antimicrobial activity of natural extraction using the synthetic ultrasmall metal nanoparticles , 2015, Scientific Reports.

[28]  C. Wagner,et al.  Multivalent Ligand Binding to Cell Membrane Antigens: Defining the Interplay of Affinity, Valency, and Expression Density. , 2018, Journal of the American Chemical Society.

[29]  M. I. Setyawati,et al.  Novel theranostic DNA nanoscaffolds for the simultaneous detection and killing of Escherichia coli and Staphylococcus aureus. , 2014, ACS applied materials & interfaces.

[30]  Kersten S. Rabe,et al.  Orthogonal protein decoration of DNA origami. , 2010, Angewandte Chemie.

[31]  P. Eaton,et al.  Silver nanoparticle stabilized by hydrolyzed collagen and natural polymers: Synthesis, characterization and antibacterial-antifungal evaluation. , 2019, International journal of biological macromolecules.

[32]  M. Guida,et al.  Efficiency of gold nanoparticles coated with the antimicrobial peptide indolicidin against biofilm formation and development of Candida spp. clinical isolates , 2018, Infection and drug resistance.

[33]  Yao Wu,et al.  Bottlebrush-like highly efficient antibacterial coating constructed using α-helical peptide dendritic polymers on the poly(styrene-b-(ethylene-co-butylene)-b-styrene) surface. , 2020, Journal of materials chemistry. B.

[34]  J. Turkevich,et al.  Colloidal gold. Part II , 1985 .

[35]  T. Xu,et al.  Evaluation of polyamidoamine (PAMAM) dendrimers as drug carriers of anti-bacterial drugs using sulfamethoxazole (SMZ) as a model drug. , 2007, European journal of medicinal chemistry.

[36]  F. Albericio,et al.  Carbosilane Dendron-Peptide Nanoconjugates as Antimicrobial Agents. , 2019, Molecular pharmaceutics.

[37]  R. Hancock.  Cationic antimicrobial peptides: towards clinical applications , 2000, Expert opinion on investigational drugs.

[38]  Jia-You Fang,et al.  Nano-Based Drug Delivery or Targeting to Eradicate Bacteria for Infection Mitigation: A Review of Recent Advances , 2020, Frontiers in Chemistry.

[39]  J. Storsberg,et al.  The impact of multivalence and self-assembly in the design of polymeric antimicrobial peptide mimics. , 2020, ACS applied materials & interfaces.

[40]  Masayuki Endo,et al.  Sequence-selective single-molecule alkylation with a pyrrole-imidazole polyamide visualized in a DNA nanoscaffold. , 2012, Journal of the American Chemical Society.

[41]  Aziza M. Hassan,et al.  Nanoformulation of Biogenic Cefotaxime-Conjugated-Silver Nanoparticles for Enhanced Antibacterial Efficacy Against Multidrug-Resistant Bacteria and Anticancer Studies , 2020, International journal of nanomedicine.

[42]  Anna F. A. Peacock,et al.  Polymyxin B containing polyion complex (PIC) nanoparticles: Improving the antimicrobial activity by tailoring the degree of polymerisation of the inert component , 2017, Scientific Reports.

[43]  J. M. Lanao,et al.  Current applications of nanoparticles in infectious diseases. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[44]  Mario Ficker,et al.  Synthesis and Antimicrobial Properties of a Ciprofloxacin and PAMAM-dendrimer Conjugate , 2020, Molecules.

[45]  K. Sharpless,et al.  Reengineering Antibiotics to Combat Bacterial Resistance: Click Chemistry [1,2,3]-Triazole Vancomycin Dimers with Potent Activity against MRSA and VRE. , 2017, Chemistry.

[46]  M. Teplova,et al.  Internal derivatization of oligonucleotides with selenium for X-ray crystallography using MAD. , 2002, Journal of the American Chemical Society.

[47]  R. Cavalli,et al.  Review Nanoparticulate delivery systems for antiviral drugs , 2010 .

[48]  Veikko Linko,et al.  Structural stability of DNA origami nanostructures under application-specific conditions , 2018, Computational and structural biotechnology journal.

[49]  Shaobing Zhou,et al.  Advances in cell penetrating peptides and their functionalization of polymeric nanoplatforms for drug delivery. , 2020, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[50]  J. Tam,et al.  Peptide dendrimers: applications and synthesis. , 2002, Journal of biotechnology.

[51]  Mateus Borba Cardoso,et al.  Defeating Bacterial Resistance and Preventing Mammalian Cells Toxicity Through Rational Design of Antibiotic-Functionalized Nanoparticles , 2017, Scientific Reports.

[52]  C. Tung,et al.  A Water-Stable Cl@Ag14 Cluster Based Metal-Organic Open Framework for Dichromate Trapping and Bacterial Inhibition. , 2017, Inorganic chemistry.

[53]  Thommey P. Thomas,et al.  Dendrimer-based multivalent vancomycin nanoplatform for targeting the drug-resistant bacterial surface. , 2013, ACS nano.

[54]  Robert E. W. Hancock,et al.  Multifunctional cationic host defence peptides and their clinical applications , 2011, Cellular and Molecular Life Sciences.

[55]  S. Rimpelová,et al.  Porphyrin‑silver nanoparticles hybrids: Synthesis, characterization and antibacterial activity. , 2019, Materials science & engineering. C, Materials for biological applications.

[56]  Eiji Nakata,et al.  Zinc-finger proteins for site-specific protein positioning on DNA-origami structures. , 2012, Angewandte Chemie.

[57]  M. Malmsten.  Interactions of Antimicrobial Peptides with Bacterial Membranes and Membrane Components. , 2015, Current topics in medicinal chemistry.

[58]  S. Alfei,et al.  Antibacterial Activity of Non-Cytotoxic, Amino Acid-Modified Polycationic Dendrimers against Pseudomonas aeruginosa and Other Non-Fermenting Gram-Negative Bacteria , 2020, Polymers.

[59]  T. L. Santos,et al.  Nanobiostructure of fibrous-like alumina functionalized with an analog of the BP100 peptide: Synthesis, characterization and biological applications. , 2018, Colloids and surfaces. B, Biointerfaces.

[60]  M. Rai,et al.  Silver nanoparticles as a new generation of antimicrobials. , 2009, Biotechnology advances.

[61]  Analette I. Lopez,et al.  Antibacterial activity and cytotoxicity of PEGylated poly(amidoamine) dendrimers. , 2009, Molecular bioSystems.

[62]  N. Seeman.  Construction of three-dimensional stick figures from branched DNA. , 1991, DNA and cell biology.

[63]  N. Chandrasekaran,et al.  Enhanced activity of lysozyme-AgNP conjugate with synergic antibacterial effect without damaging the catalytic site of lysozyme , 2014, Artificial cells, nanomedicine, and biotechnology.

[64]  Avishek Kumar,et al.  Eco-friendly nanocomposites derived from geranium oil and zinc oxide in one step approach , 2019, Scientific Reports.

[65]  Ismail Ab Rahman,et al.  Synthesis of silica nanoparticles by sol-gel: size-dependent properties, surface modification, and applications in silica-polymer nanocomposites — a review , 2012 .

[66]  Michael Malkoch,et al.  Simplifying the synthesis of dendrimers: accelerated approaches. , 2012, Chemical Society reviews.

[67]  A. Curtis,et al.  Application of Nanoparticle Technologies in the Combat against Anti-Microbial Resistance , 2018, Pharmaceutics.

[68]  Tsung-Rong Kuo,et al.  Antimicrobial Gold Nanoclusters: Recent Developments and Future Perspectives , 2019, International journal of molecular sciences.

[69]  N. Seeman.  Nucleic acid junctions and lattices. , 1982, Journal of theoretical biology.

[70]  Hu Yang,et al.  Penicillin V-conjugated PEG-PAMAM star polymers , 2003, Journal of biomaterials science. Polymer edition.

[71]  J. Duan,et al.  Potent Antibacterial Nanoparticles against Biofilm and Intracellular Bacteria , 2016, Scientific Reports.

[72]  Baoquan Ding,et al.  A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo , 2018, Nature Biotechnology.

[73]  E. Zubarev,et al.  Therapeutic platforms based on gold nanoparticles and their covalent conjugates with drug molecules. , 2013, Advanced drug delivery reviews.

[74]  G. Maiorano,et al.  Biomimetic Nanocarriers for Cancer Target Therapy , 2020, Bioengineering.

[75]  Qiao Jiang,et al.  DNA origami as an in vivo drug delivery vehicle for cancer therapy. , 2014, ACS nano.

[76]  A. Ulrich,et al.  Antibiotic gold: tethering of antimicrobial peptides to gold nanoparticles maintains conformational flexibility of peptides and improves trypsin susceptibility. , 2017, Biomaterials science.

[77]  Jill M. Steinbach-Rankins,et al.  Peptide-modified nanoparticles inhibit formation of Porphyromonas gingivalis biofilms with Streptococcus gordonii , 2017, International journal of nanomedicine.

[78]  S. G. Harroun,et al.  Self‐Assembly of Antimicrobial Peptides on Gold Nanodots: Against Multidrug‐Resistant Bacteria and Wound‐Healing Application , 2015 .

[79]  R. Hancock,et al.  Antibacterial peptides for therapeutic use: obstacles and realistic outlook. , 2006, Current opinion in pharmacology.

[80]  Anirban Bhunia,et al.  Enhanced stability and activity of an antimicrobial peptide in conjugation with silver nanoparticle. , 2016, Journal of colloid and interface science.

[81]  M. Martins,et al.  The potential utility of chitosan micro/nanoparticles in the treatment of gastric infection , 2014, Expert review of anti-infective therapy.

[82]  Songhang Li,et al.  Tetrahedral Framework Nucleic Acids Deliver Antimicrobial Peptides with Improved Effects and Less Susceptibility to Bacterial Degradation. , 2020, Nano letters.