Elsevier

Progress in Polymer Science

Volume 76, January 2018, Pages 40-64
Progress in Polymer Science

Antimicrobial polymeric nanoparticles

https://doi.org/10.1016/j.progpolymsci.2017.07.007Get rights and content

Abstract

Currently, infections caused by multidrug-resistant bacteria have reached critical levels. Thus, various approaches are being explored for the development of new and effective antimicrobial agents, one of which lies in the form of polymeric nanoparticles. Driven by the significant advancements in controlled polymerization techniques over the last few decades, antimicrobial polymeric nanoparticles have recently been investigated as potential new antibiotics to combat the rise of infectious diseases. This review aims at presenting an overview of the history and state-of-the-art of antimicrobial polymeric nanoparticles including their available structure-activity relationship, and highlights the impact of controlled polymerization has on the antimicrobial field as well as some of the key challenges that still need to be overcome for potential clinical applications. Herein, potential new developments are suggested as well.

Introduction

Recently, the World Health Organization (WHO) revealed that the threat of antibiotic resistance has reached critical levels worldwide [1]. Specifically, WHO has identified 12 emerging superbugs that are resistant to many antibiotics as priority targets to combat, grouping them into three categories: critical, high, and medium. For instance, carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa were listed as critical, methicillin-resistant Staphylococcus aureus (MRSA) can be found in the high category, whereas ampicillin-resistant Haemophilus influenza was classified as medium [2]. Coupled with the lack of new product discovery due to the near-complete screening of available natural resources, the world is facing the risk of reverting back to the ‘medical dark ages’ (i.e., the pre-antibiotic era). Many world governments thus recognize the urgent need for new solutions to combat this global healthcare issue. Driven by the significant advancements in controlled polymerization techniques [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], that have enabled the production of nanomaterials with tailorable biological properties for a wide range of biomedical applications [15], [16], [17], [18], [19], [20], [21], [22], [23], synthetic polymers potentially represent a promising approach to curb the rise of antibiotic resistance. In fact, there are various examples in literature that describe the synthesis of linear polymers with antimicrobial properties [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], mostly by mimicking the chemical structure of antimicrobial peptides (AMPs), while others include the conjugation of synthetic polymers with conventional antibiotics (to improve pharmacokinetics for instance) [36], [37], [38].

However, there has been growing interest recently in the development of antimicrobial polymeric nanoparticles. This is because the formulation of polymers into nanoparticles (e.g., micelles, vesicles, star polymers, and inorganic-polymer hybrids) of various shapes and sizes has been shown to yield many advantages over linear polymers in other targeted applications such as drug/gene delivery [39], [40], [41], [42]. For instance, a main advantage is the multivalency of polymeric nanoparticles, where the presentation of a cluster of (multiple) functional groups from a nanoparticle construct enables higher cell recognition and binding capabilities compared to linear polymers [43], [44]. In addition, polymer nanoparticles like micelles, vesicles or star polymers allow for the efficient encapsulation of cargo molecules that can be released at targeted sites [45], [46], [47], [48]. Furthermore, the fabrication of inorganic-polymer hybrid nanoparticles provides new avenues for synergistic therapy (e.g., photodynamic therapy) and/or diagnostic purposes (e.g., biosensing) [49], [50], [51].

In this review, we present an overview of the history and recent advances of polymeric nanoparticles that have been applied in the antimicrobial field where some of these nanoparticles have been demonstrated to be effective against the pathogens specified above by WHO. Specifically, the review focuses on the development of polymeric nanoparticles that demonstrate inherent antimicrobial properties (i.e., the nanoparticle acts as the active antimicrobial agent) and highlights any structural-activity relationship that will aid our understanding on the rational design of polymer-based antimicrobial agents.

Section snippets

Polymer nanoparticles as active antimicrobial agents

By mimicking the general chemical structure of naturally-occurring AMPs [52], synthetic polymers could be endowed with intrinsic antimicrobial activity by incorporating cationic and hydrophobic moieties into the polymer chains [27], [53]. The overall cationic charge of the polymer enables interaction with bacterial cell walls that are typically negatively charged, while the hydrophobic counterparts facilitate microbial membrane penetration [27]. It should be noted, however, that antimicrobial

Summary and future outlook

In the last few years, we have witnessed an increasing number of publications that describe new and innovative strategies to combat the rise of multidrug-resistant bacteria using polymer nanoparticles made via controlled polymerization techniques. This review highlighted the history and recent advances of antimicrobial polymeric nanoparticles as new alternatives to conventional antibiotics, where the nanoparticles possess inherent bactericidal properties. To date, almost every antimicrobial

Acknowledgements

GGQ and CB acknowledge financial support provided by the Australian Research Council (ARC) via the Discovery Project (DP160101312, DP170104321) and Future Fellowship (FT120100096) schemes, respectively. SJL acknowledges the Australian Government for providing an International Postgraduate Research Scholarship (IPRS) and an Australian Postgraduate Award (APAInt). EHHW acknowledges the receipt of 2016 UNSW Vice-Chancellor’s Research Fellowship from UNSW Australia.

References (195)

  • H. Takahashi et al.

    Synthetic random copolymers as a molecular platform to mimic host-defense antimicrobial peptides

    Bioconjug Chem

    (2017)
  • N.D. Stebbins et al.

    Antibiotic-containing polymers for localized, sustained drug delivery

    Adv Drug Deliv Rev

    (2014)
  • T.K. Nguyen et al.

    Co-delivery of nitric oxide and antibiotic using polymeric nanoparticles

    Chem Sci

    (2016)
  • M. Callari et al.

    Polymers with platinum drugs and other macromolecular metal complexes for cancer treatment

    Prog Polym Sci

    (2014)
  • M. Ahmed et al.

    Progress of RAFT based polymers in gene delivery

    Prog Polym Sci

    (2013)
  • Y. Zhu et al.

    Polymer vesicles: mechanism, preparation, application, and responsive behavior

    Prog Polym Sci

    (2017)
  • R. Palao-Suay et al.

    Self-assembling polymer systems for advanced treatment of cancer and inflammation

    Prog Polym Sci

    (2016)
  • W. Wu et al.

    Star polymers: advances in biomedical applications

    Prog Polym Sci

    (2015)
  • Z.L. Tyrrell et al.

    Fabrication of micellar nanoparticles for drug delivery through the self-assembly of block copolymers

    Prog Polym Sci

    (2010)
  • J.K. Oh et al.

    The development of microgels/nanogels for drug delivery applications

    Prog Polym Sci

    (2008)
  • H. Wang et al.

    The efficacy of self-assembled cationic antimicrobial peptide nanoparticles against Cryptococcus neoformans for the treatment of meningitis

    Biomaterials

    (2010)
  • V. Taresco et al.

    Antimicrobial and antioxidant amphiphilic random copolymers to address medical device-centered infections

    Acta Biomater

    (2015)
  • Y. Qiao et al.

    Highly dynamic biodegradable micelles capable of lysing Gram-positive and Gram-negative bacterial membrane

    Biomaterials

    (2012)
  • Y. Li et al.

    Polyion complex micellar nanoparticles for integrated fluorometric detection and bacteria inhibition in aqueous media

    Biomaterials

    (2014)
  • Y. Xi et al.

    Preparation and antibacterial mechanism insight of polypeptide-based micelles with excellent antibacterial activities

    Biomacromolecules

    (2016)
  • B. Hisey et al.

    Phosphonium-Functionalized polymer micelles with intrinsic antibacterial activity

    Biomacromolecules

    (2017)
  • Anonymous et al.

    Antimicrobial Resistance Global Report on Surveillance

    (2014)
  • C. Willyard

    The drug-resistant bacteria that pose the greatest health threats

    Nature

    (2017)
  • C. Boyer et al.

    Copper-mediated living radical polymerization (atom transfer radical polymerization and copper(0) mediated polymerization): from fundamentals to bioapplications

    Chem Rev

    (2016)
  • G. Moad et al.

    RAFT polymerization and some of its applications

    Chem Asian J

    (2013)
  • G. Moad et al.

    Living radical polymerization by the RAFT process – a third update

    Aust J Chem

    (2012)
  • K. Matyjaszewski

    Atom transfer radical polymerization (ATRP): current status and future perspectives

    Macromolecules

    (2012)
  • N.E. Kamber et al.

    Organocatalytic ring-opening polymerization

    Chem Rev

    (2007)
  • C.J. Hawker et al.

    New polymer synthesis by nitroxide mediated living radical polymerizations

    Chem Rev

    (2001)
  • M. Kamigaito et al.

    Metal-catalyzed living radical polymerization

    Chem Rev

    (2001)
  • I. Cobo et al.

    Smart hybrid materials by conjugation of responsive polymers to biomacromolecules

    Nat Mater

    (2015)
  • E.M. Pelegri-O'Day et al.

    Therapeutic protein-polymer conjugates: advancing beyond PEGylation

    J Am Chem Soc

    (2014)
  • W.L. Brooks et al.

    Synthesis and applications of boronic acid-containing polymers: from materials to medicine

    Chem Rev

    (2016)
  • A. Dong et al.

    Chemical insights into antibacterial N-halamines

    Chem Rev

    (2017)
  • Y. Wo et al.

    Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO)

    Biomater Sci

    (2016)
  • F. Sgolastra et al.

    Designing mimics of membrane active proteins

    Acc Chem Res

    (2013)
  • G.N. Tew et al.

    De novo design of antimicrobial polymers, foldamers, and small molecules: from discovery to practical applications

    Acc Chem Res

    (2010)
  • K. Kuroda et al.

    Antimicrobial polymers as synthetic mimics of host-defense peptides

    Nanomed Nanobiotechnol

    (2013)
  • K. Lienkamp et al.

    Synthetic mimics of antimicrobial peptides – a versatile ring-opening metathesis polymerization based platform for the synthesis of selective antibacterial and cell-penetrating polymers

    Chem Eur J

    (2009)
  • K. Lienkamp et al.

    Antimicrobial polymers prepared by ring-opening metathesis polymerization: manipulating antimicrobial properties by organic counterion and charge density variation

    Chem Eur J

    (2009)
  • G.J. Gabriel et al.

    Comparison of facially amphiphilic versus segregated monomers in the design of antibacterial copolymers

    Chem Eur J

    (2009)
  • H. Takahashi et al.

    Cationic amphiphilic polymers with antimicrobial activity for oral care applications: eradication of S. mutans biofilm

    Biomacromolecules

    (2017)
  • M. Alvarez-Paino et al.

    Antimicrobial polymers in the nano-world

    Nanomaterials

    (2017)
  • W. Ren et al.

    Developments in antimicrobial polymers

    J Polym Sci Part A Polym Chem

    (2017)
  • A. Al-Ahmad et al.

    Nature-inspired antimicrobial polymers?assessment of their potential for biomedical applications

    PLoS One

    (2013)
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    These authors contributed equally to the manuscript.

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