Antimicrobial polymeric nanoparticles
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.
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These authors contributed equally to the manuscript.