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Activatable Type‐I Photosensitizer with Quenched Photosensitization Pre and Post Photodynamic Therapy

Von Wiley-VCH zur Verfügung gestellt

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 approach is 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 photosensitizers 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 the side effect and improving the therapeutic effect. With promising results in in vitro and in vivo tumor treatment, this presented strategy will pave way for the design of more on-demand switchable photosensitizers with minimized side effects in future.

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