Biodegradable Antibacterial Polymeric Nanosystems: A New Hope to Cope with Multidrug-Resistant Bacteria

The human society is faced with daunting threats from bacterial infections. Over decades, a variety of antibacterial polymeric nanosystems have exhibited great promise for the eradication of multidrug-resistant bacteria and persistent biofilms by enhancing bacterial recognition and binding capabilities. In this Review, the "state-of-the-art" biodegradable antibacterial polymeric nanosystems, which could respond to bacteria environments (e.g., acidity or bacterial enzymes) for controlled antibiotic release or multimodal antibacterial treatment, are summarized. The current antibacterial polymeric nanosystems can be categorized into antibiotic-containing and intrinsic antibacterial nanosystems. The antibiotic-containing polymeric nanosystems include antibiotic-encapsulated nanocarriers (e.g., polymeric micelles, vesicles, nanogels) and antibiotic-conjugated polymer nanosystems for the delivery of antibiotic drugs. On the other hand, the intrinsic antibacterial polymer nanosystems containing bactericidal moieties such as quaternary ammonium groups, phosphonium groups, polycations, antimicrobial peptides (AMPs), and their synthetic mimics, are also described. The biodegradability of the nanosystems can be rendered by the incorporation of labile chemical linkages, such as carbonate, ester, amide, and phosphoester bonds. The design and synthesis of the degradable polymeric building blocks and their fabrications into nanosystems are also explicated, together with their plausible action mechanisms and potential biomedical applications. The perspectives of the current research in this field are also described.