Journal
ACS NANO
Volume 9, Issue 11, Pages 11064-11074Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b04501
Keywords
near-infrared; nanophotosensitizer; reactive oxygen species; domino effect; cancer therapy
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Funding
- 973 Program [2013CB933800]
- National Natural Science Foundation of China [21535004, 21227005, 21390411, 21422505, 21375081, 21505087]
- Natural Science Foundation for Distinguished Young Scholars of Shandong Province [JQ201503]
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Photodynamic therapy (PDT) is a well-established modality for cancer therapy, which locally kills cancer cells when light irradiates a photosensitizer. However, conventional PDT is often limited by the extremely short lifespan and severely limited diffusion distance of reactive oxygen species (ROS) generated by photosensitizer, as well as the penetration depth of visible light activation. Here, we develop a near-infrared (NIR) triggered nanophotosensitizer based on mitochondria targeted titanium dioxide-coated upconversion nanoparticles for PDT against cancer. When irradiated by NIR laser, the nanophotosensitizer could produce ROS in mitochondria, which induced the domino effect on ROS burst. The overproduced ROS accumulated in mitochondria, resulting in mitochondrial collapse and irreversible cell apoptosis. Confocal fluorescence imaging indicated that the mitochondrial targeting and real-time imaging of ROS burst could be achieved in living cells. The complete removal of tumor in vivo confirmed the excellent therapeutic effect of the nanophotosensitizer.
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