Antibiotic resistance due to suboptimal targeting and inconsistent antibiotic release at bacterial infection sites has driven the formulation of stimuli‐responsive nanocarriers for antibacterial therapy. Unlike conventional nanocarriers, stimuli‐responsive nanocarriers have the ability to specifically enhance targeting and drug release profiles. There has been a significant escalation in the design and development of novel nanomaterials worldwide; in particular, intrinsic stimuli‐responsive antibiotic nanocarriers, due to their enhanced activity, improved targeted delivery, and superior potential for bacterial penetration and eradication. Herein, we provide an extensive and critical review of pH‐, enzyme‐, redox‐, and ionic microenvironment‐responsive nanocarriers that have been reported in literature to date, with an emphasis on the mechanisms of drug release, the nanomaterials used, the nanosystems constructed and the antibacterial efficacy of the nanocarriers. The review also highlights further avenues of research for optimizing their potential and commercialization. This review confirms the potential of intrinsic stimuli‐responsive nanocarriers for enhanced drug delivery and antibacterial killing. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Rampant antimicrobial resistance calls for innovative strategies to effectively control bacterial infections, enhance antibacterial efficacy, minimize side effects, and protect existing antibiotics in the market. Therefore, to enhance the delivery of antibiotics and increase their bioavailability and accumulation at the site of infection, the surfaces of nano-drug delivery systems have been diversely modified. This strategy applies various covalent and non-covalent techniques to introduce specific coating materials that have been found to be effective against various sensitive and resistant microorganisms. In this review, we discuss the techniques of surface modification of nanocarriers loaded with antibacterial agents. Furthermore, saccharides, polymers, peptides, antibiotics, enzymes and cell membranes coatings that have been used for surface functionalization of nano-drug delivery systems are described, emphasizing current approaches for enhancing delivery, bioavailability, and efficacy of surfacemodified antibacterial nanocarriers at infection sites. This article offers a critical overview of the potential of surface-modified antibacterial nanocarriers to overcome the limitations of conventional antibiotics in the treatment of bacterial infections.

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