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WIREs Nanomed Nanobiotechnol
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Intrinsic stimuli‐responsive nanocarriers for smart drug delivery of antibacterial agents—An in‐depth review of the last two decades

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Abstract 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
Limitations of conventional dosage drug forms can be addressed by stimuli‐responsive nanocarriers
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Intrinsic stimuli‐responsive nanocarriers (left) that have been developed for the treatment of various bacteria (right) over the last two decades
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Mechanism of the action of intrinsic stimuli‐responsive antibacterial‐releasing nanogel
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Scheme illustrating the production of HC‐NPs (Cortese et al., 2019)
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Scheme showing the mesoporous silica nanoparticles loaded with gentamicin and mesoporous channels decorated with bacteria toxin‐sensitive liposomes and UBI2 for intracellular antibiotic delivery (Yang et al., 2018)
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Evolution over time of enzyme‐responsive nanocarriers of antibacterial agents (Baier et al., 2013; M. Chen, Xie, et al., 2018; Cortese et al., 2019; Li et al., 2016; Thamphiwatana et al., 2014; M.‐H. Xiong, Bao, et al., 2012; M. H. Xiong, Li, et al., 2012; Yang et al., 2018; C. Y. Zhang et al., 2018)
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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