Hypoxia Induced by Upconversion‐Based Photodynamic Therapy: Towards Highly Effective Synergistic Bioreductive Therapy in Tumors |
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| Authors: | Dr. Yanyan Liu Prof. Yong Liu Prof. Wenbo Bu Dr. Chao Cheng Dr. Changjing Zuo Dr. Qingfeng Xiao Yong Sun Dr. Dalong Ni Dr. Chen Zhang Dr. Jianan Liu Prof. Jianlin Shi |
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| Affiliation: | 1. State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding‐xi Road, Shanghai 200050 (P.R. China);2. Cancer Research Institute, Shanghai Cancer Hospital, Fudan University, 270 Dong‐an Road, Shanghai 200032 (P.R. China);3. Department of Nuclear Medicine, Changhai Hospital of Shanghai, 168 Chang‐hai Road, Shanghai 200433 (P.R. China) |
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| Abstract: | Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro‐drugs that can be activated at low‐oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica‐shelled upconversion nanoparticles (UCNPs) nanostructure capable of co‐delivering photosensitizer (PS) molecules and a bioreductive pro‐drug (tirapazamine, TPZ) were designed (TPZ‐UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC‐based (UC‐) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC‐PDT. Treatment with TPZ‐UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC‐PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much‐enhanced cytotoxicity of TPZ under PDT‐induced hypoxia. |
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| Keywords: | bioreductive pro‐drugs hypoxia photodynamic therapy synergetic therapy upconversion nanoparticles |
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