Stimuli-responsive nanocarriers for precision targeted and controlled antimicrobial drug delivery in drug-resistant infections
- 1Clinical Laboratory, Danyang Hospital of Traditional Chinese Medicine
Abstract
. Conventional antibiotics exhibit non-specific systemic distribution, frequently fail to achieve sustained therapeutic concentrations at infection sites, and expose both pathogenic and commensal microbiota to sub-inhibitory levels that accelerate resistance selection. In contrast, infected tissues exhibit distinct and dynamic microenvironmental features-including acidic pH, elevated reactive oxygen species, pathogen-associated enzymatic activity, hypoxia, and localized inflammatory signaling-that are largely absent in healthy tissues and provide exploitable triggers for targeted therapy. Stimuli-responsive nanocarriers are engineered to sense and respond to these pathological cues, enabling spatiotemporally controlled and infection-specific drug release while minimizing systemic exposure. In this review, we systematically analyze the mechanistic foundations of pH-, enzyme-, redox-, and multi-stimuli-responsive nanocarriers, with particular emphasis on how trigger-induced physicochemical transformations govern drug retention, activation, penetration, and release within drug-resistant infection niches. We further examine how these platforms address key resistance-associated barriers, including impaired tissue penetration, biofilm-associated tolerance, intracellular pathogen persistence, efflux-mediated drug extrusion, and enzymatic antibiotic degradation. Importantly, we provide a critical comparison between passive nanocarriers, stimuli-responsive systems, and free antibiotics, highlighting the conditions under which infection-synchronized delivery enhances antimicrobial efficacy, reduces off-target toxicity, and mitigates resistance-selective pressure. We also evaluate current translational challenges, including microenvironmental heterogeneity, trigger variability, long-term safety, scalable manufacturing, and regulatory complexity. Collectively, stimuli-responsive nanocarriers represent a paradigm shift from passive systemic exposure toward context-aware, site-selective antimicrobial intervention, offering a promising strategy to overcome persistent limitations in anti-infective therapy and address AMR beyond the pace of conventional antibiotic discovery.
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BibTeX
@article{dai2026stimuliresponsive,
title = {{Stimuli-responsive nanocarriers for precision targeted and controlled antimicrobial drug delivery in drug-resistant infections}},
author = {Li Dai and Xiaoyan Sun},
journal = {Frontiers in Microbiology},
year = {2026},
month = jun,
doi = {10.3389/fmicb.2026.1803769},
url = {https://doi.org/10.3389/fmicb.2026.1803769},
note = {CC BY},
}
RIS
TY - JOUR
TI - Stimuli-responsive nanocarriers for precision targeted and controlled antimicrobial drug delivery in drug-resistant infections
AU - Li Dai
AU - Xiaoyan Sun
PY - 2026
DA - 2026/06/12
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1803769
UR - https://doi.org/10.3389/fmicb.2026.1803769
AB - . Conventional antibiotics exhibit non-specific systemic distribution, frequently fail to achieve sustained therapeutic concentrations at infection sites, and expose both pathogenic and commensal microbiota to sub-inhibitory levels that accelerate resistance selection. In contrast, infected tissues exhibit distinct and dynamic microenvironmental features-including acidic pH, elevated reactive oxygen species, pathogen-associated enzymatic activity, hypoxia, and localized inflammatory signaling-that are largely absent in healthy tissues and provide exploitable triggers for targeted therapy. Stimuli-responsive nanocarriers are engineered to sense and respond to these pathological cues, enabling spatiotemporally controlled and infection-specific drug release while minimizing systemic exposure. In this review, we systematically analyze the mechanistic foundations of pH-, enzyme-, redox-, and multi-stimuli-responsive nanocarriers, with particular emphasis on how trigger-induced physicochemical transformations govern drug retention, activation, penetration, and release within drug-resistant infection niches. We further examine how these platforms address key resistance-associated barriers, including impaired tissue penetration, biofilm-associated tolerance, intracellular pathogen persistence, efflux-mediated drug extrusion, and enzymatic antibiotic degradation. Importantly, we provide a critical comparison between passive nanocarriers, stimuli-responsive systems, and free antibiotics, highlighting the conditions under which infection-synchronized delivery enhances antimicrobial efficacy, reduces off-target toxicity, and mitigates resistance-selective pressure. We also evaluate current translational challenges, including microenvironmental heterogeneity, trigger variability, long-term safety, scalable manufacturing, and regulatory complexity. Collectively, stimuli-responsive nanocarriers represent a paradigm shift from passive systemic exposure toward context-aware, site-selective antimicrobial intervention, offering a promising strategy to overcome persistent limitations in anti-infective therapy and address AMR beyond the pace of conventional antibiotic discovery.
SN - 1664-302X
ER -