Precision Phototherapy Enabled by Decoding Complex Microenvironments

作者：Qihang Ding, Manlin Qi, Wen Li, Meiqi Li, Jie Xu, Yujin Kim, Goeun Kim, Biao Dong, Lin Wang, Jong Seung Kim · 发表于：Accounts of Chemical Research · 年份：2025 · DOI：10.1021/acs.accounts.5c00488 · 被引用次数：33 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Photoacoustic and Ultrasonic Imaging

Conspectus The complex and dynamic microenvironments of pathological sites, including infections, tumors, and neurological disorders, impose formidable challenges on conventional therapies due to features such as iron dysregulation, localized acidity, biofilm barriers, and thermal adaptation. Harnessing these microenvironmental cues to design light-activated, microenvironment-responsive therapeutic platforms offers a promising strategy for precise, spatiotemporally controlled treatments. Nutritional immunity restricts iron availability to suppress pathogen proliferation, while bacteria deploy specialized siderophore-mediated uptake systems to circumvent this restriction. By exploiting this vulnerability, “Trojan horse” nanoplatforms such as a multifunctional nanocomposite (Ga-CT@P) can hijack bacterial iron uptake pathways, induce iron starvation, and exert potent antimicrobial effects. DFT calculations revealed that Ga 3+ exhibits stronger, more uniform binding to enterobactin than Fe 3+, leading to stable, redox-inert complexes that mislead bacterial transport systems. Beyond metal ion interference, acid-responsive photodynamic therapy (PDT) offers spatiotemporally precise activation at infectious sites while minimizing off-target toxicity. Our development of DHTPA, a pH-responsive AIE photosensitizer, enables robust reactive oxygen species (ROS) generation exclusively under mildly acidic conditions, enhancing bactericidal efficacy. This platform demonstrated strong antibac...