“Three birds with one stone” nanoplatform: Efficient near‐infrared‐triggered type‑I AIE photosensitizer for mitochondria‐targeted photodynamic therapy against hypoxic tumors
Shengnan Liu,
Yu Pei,
Yan Sun,
Ziwei Wang,
Haoran Chen,
Dongxia Zhu,
Martin R. Bryce,
Ben Zhong Tang,
Yulei Chang
Affiliations
Shengnan Liu
Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province Department of Chemistry Northeast Normal University Changchun Jilin Province People's Republic of China
Yu Pei
Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province Department of Chemistry Northeast Normal University Changchun Jilin Province People's Republic of China
Yan Sun
Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province Department of Chemistry Northeast Normal University Changchun Jilin Province People's Republic of China
Ziwei Wang
Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province Department of Chemistry Northeast Normal University Changchun Jilin Province People's Republic of China
Haoran Chen
State Key Laboratory of Luminescence and Applications Changchun Institute of Optics Fine Mechanics and Physics Chinese Academy of Sciences Changchun Jilin Province People's Republic of China
Dongxia Zhu
Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province Department of Chemistry Northeast Normal University Changchun Jilin Province People's Republic of China
Martin R. Bryce
Department of Chemistry Durham University Durham UK
Ben Zhong Tang
Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction State Key Laboratory of Molecular Neuroscience Division of Life Science Ming Wai Lau Centre for Reparative Medicine Karolinska Institute and Guangdong‐Hong Kong‐Macau Joint Laboratory of Optoelectronic and Magnetic Functional Materials The Hong Kong University of Science and Technology Kowloon Hong Kong People's Republic of China
Yulei Chang
State Key Laboratory of Luminescence and Applications Changchun Institute of Optics Fine Mechanics and Physics Chinese Academy of Sciences Changchun Jilin Province People's Republic of China
Abstract Currently three major problems seriously limit the practical application of cancer photodynamic therapy (PDT): (i) the hypoxic tumor microenvironment (TME); (ii) low generation efficiency of toxic reactive oxygen species (ROS) in aggregates and (iii) shallow tissue penetration depth of excitation light. Very limited approaches are available for addressing all the above three problems with a single design. Herein, a rational “three birds with one stone” molecular and nanoengineering strategy is demonstrated: a photodynamic nanoplatform U‐Ir@PAA‐ABS based on the covalent combination of lanthanide‐doped upconversion nanoparticles (UCNPs) and an AIE‐active dinuclear Ir(III) complex provides a low oxygen concentration‐dependent type‐I photochemical process upon 980 nm irradiation by Föster resonance energy transfer (FRET). U‐Ir@PAA‐ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation, inducing a dual‐mode cell death mechanism by apoptosis and ferroptosis. Taken together, the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors.
