Activatable Type I Photosensitizer with Quenched Photosensitization Pre and Post Photodynamic Therapy |
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Authors: | Jianwu Tian Bowen Li Fu Zhang Zhuo Yao Wentao Song Yufu Tang Yuan Ping Bin Liu |
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Affiliation: | 1. Department of Chemical and Biomolecular Engineering, National University of Singapore, 5 A Engineering Drive 1, Singapore, 117411 Singapore These authors contributed equally to this work.;2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China;3. Department of Chemical and Biomolecular Engineering, National University of Singapore, 5 A Engineering Drive 1, Singapore, 117411 Singapore |
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Abstract: | The phototoxicity of photosensitizers (PSs) pre and post photodynamic therapy (PDT), and the hypoxic tumor microenvironment are two major problems limiting the application of PDT. While activatable PSs can successfully address the PS phototoxicity pre PDT, and type I PS can generate reactive oxygen species (ROS) effectively in hypoxic environment, very limited approaches are available for addressing the phototoxicity post PDT. There is virtually no solution available to address all these issues using a single design. Herein, we propose a proof-of-concept on-demand switchable photosensitizer with quenched photosensitization pre and post PDT, which could be activated only in tumor hypoxic environment. Particularly, a hypoxia-normoxia cycling responsive type I PS TPFN-AzoCF3 was designed to demonstrate the concept, which was further formulated into TPFN-AzoCF3 nanoparticles (NPs) using DSPE-PEG-2000 as the encapsulation matrix. The NPs could be activated only in hypoxic tumors to generate type I ROS during PDT treatment, but remain non-toxic in normal tissues, pre or after PDT, thus minimizing side effects and improving the therapeutic effect. With promising results in in vitro and in vivo tumor treatment, this presented strategy will pave the way for the design of more on-demand switchable photosensitizers with minimized side effects in the future. |
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Keywords: | Hypoxia On-Demand Switchable Photosensitizer Photodynamic Therapy Reversible Type I Photosensitizer |
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