Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 27, Pages 14945-14953Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202017350
Keywords
aggregation-induced emission (AIE); in vivo photosensitizer synthesis; metal-organic frameworks (MOFs); mitochondria-targeting; photodynamic therapy
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This study presents a cancer-cell-activated photosensitizer synthesis strategy to selectively synthesize efficient PS with mitochondria-targeting capability for potent cancer-cell-specific ablation under light irradiation, ensuring high specificity and safety for post-treatment.
Maximization of phototoxic damage on tumor with minimized side effect on normal tissue is essential for effective anticancer photodynamic therapy (PDT). This requires highly cancer-cell-specific or even cancer-cell-organelle-specific synthesis or delivery of efficient photosensitizers (PSs) in vitro and in vivo, which is difficult to achieve. Herein, we report a strategy of cancer-cell-activated PS synthesis, by which an efficient mitochondria-targeting photosensitizer with aggregation-induced-emission (AIE) feature can be selectively synthesized as an efficient image-guided PDT agent inside cancer cells. MOF-199, a Cu-II-based metal-organic framework, was selected as an inert carrier to load the PS precursors for efficient delivery and served as a Cu-I catalyst source for in situ click reaction to form PSs exclusively in cancer cells. The in situ synthesized PS showed mitochondria-targeting capability, allowing potent cancer-cell-specific ablation under light irradiation. The high specificity of PSs produced in cancer cells also makes it safer post-treatment.
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