Research Article


2016, 9(11): 3257–3266


Upconversion nano-photosensitizer targeting into mitochondria for cancer apoptosis induction and cyt c fluorescence monitoring

Yanyan Liu1, Jiawen Zhang2, Changjing Zuo3 (*), Zhen Zhang4, Dalong Ni1, Chen Zhang1, Jing Wang2, Hui Zhang4, Zhenwei Yao2, and Wenbo Bu1,5 (*)

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1 State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China
2 Department of Radiology, Huashan Hospital, Fudan University, 12 Urumqi Zhong Road, Shanghai 200040, China
3 Department of Nuclear Medicine, Changhai Hospital of Shanghai, 168 Changhai Road, Shanghai 200433, China
4 Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China
5 Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663 Zhongshan North Road, Shanghai 200062, China

Keywords: mitochondrial reactive oxygen species (mitoROS), upconversion-based photodynamic therapy (PDT), cytochrome c (cyt c), mitochondrial apoptosis
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ABSTRACT Disruption of mitochondrial reactive oxygen species (mitoROS) plays a major role in cancer cell apoptosis. Here, we designed a core/shell-structured mitochondriatargeting upconversion-based nano-photosensitizer (TPP-UC(PS)) with a lanthanidedoped upconversion nanoparticle (UCNP) core coated by a photosensitizer (PS)-incorporated dense silica shell. Following irradiation with external nearinfrared laser (NIR), TPP-UC(PS) in mitochondria caused serious mitochondrial matrix swelling for the activated upconversion-based photodynamic therapy (UC-PDT), and the mobilization of cytochrome c (cyt c) was amplified in response to the increased mitoROS. Specifically, this heme-containing cyt c could be monitored by varying TPP-UC(PS)’s upconversion luminescence signal (UCL), which may facilitate the in situ detection of cyt c for apoptosis research. As a proof of concept, our designed TPP-UC(PS) may provide significant opportunities for controlling cancer cell apoptosis under NIR stimulation and for studying apoptosis using the dynamic UCL, which is influenced by local cyt c.
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Upconversion nano-photosensitizer targeting into mitochondria for cancer apoptosis induction and cyt c fluorescence monitoring. Nano Res. 2016, 9(11): 3257–3266

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