Abstract
Photodynamic therapy is attracting increasing attention, but how to increase its tumor-specificity remains a daunting challenge. Herein we report a theranostic probe (azo-PDT) that integrates pyropheophorbide α as a photosensitizer and a NIR fluorophore for tumor imaging. The two functionalities are linked with a hypoxic-sensitive azo group. Under normal conditions, both the phototoxicity of the photosensitizer and the fluorescence of the fluorophore are inhibited. While under hypoxic condition, the reductive cleavage of the azo group will restore both functions, leading to tumor specific fluorescence imaging and phototoxicity. The results showed that azo-PDT selectively images BEL-7402 cells under hypoxia, and simultaneously inhibits BEL-7402 cell proliferation after near-infrared irradiation under hypoxia, while little effect on BEL-7402 cell viability was observed under normoxia. These results confirm the feasibility of our design strategy to improve the tumor-targeting ability of photodynamic therapy, and presents azo-PDT probe as a promising dual functional agent.
Highlights
Photodynamic therapy is attracting increasing attention, but how to increase its tumor-specificity remains a daunting challenge
While many studies have been reported on hypoxia-activated therapeutic or imaging agents, hypoxia-dependent dual activation for simultaneous tumor imaging and photodynamic therapy has not been investigated to date, to the best of our knowledge
We chose pyropheophorbide α (Pyro), which is an analog of Photofrin, as the photosensitizer for our proof-of-concept study due to its easy availability
Summary
Photodynamic therapy is attracting increasing attention, but how to increase its tumor-specificity remains a daunting challenge. To design bifunctional probes for hypoxia-dependent tumor imaging and photodynamic therapy, we started by interrogating the mechanism by which photosensitizers convert light energy into singlet oxygen. Utilizing the FRET mechanism, we conjugated a photosensitizer (as energy donor) and a near-infrared fluorophore (as energy acceptor) with an azo group as hypoxia trigger, to successfully design a new chemical entity (azo-PDT) that can detect solid tumors based on its hypoxiaactivated fluorogenic response and show hypoxia-specific phototoxicity for the ablation of tumor cells.
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