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Structure-guided design of mitochondria-targeting near-infrared fluorophore for dual modal phototherapy

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Abstract

Mitochondria are recognized as the ideal target for cancer treatment. In this work, structure-guided design and synthesis of a mitochondria-targeted near-infrared (NIR) photosensitizer (PS) for synchronous cancer photodynamic therapy (PDT) and photothermal therapy (PTT) were performed. This multifunctional small-molecule PS is demonstrated to preferentially accumulate in cancer cells. As mitochondria is susceptible to hyperthermia and excessive reactive oxygen species, this new PS integrating PTT and PDT treatment exhibits highly efficient phototherapy in multiple cancer cells and animal xenograft models. Furthermore, this targeted PS with NIR imaging property also enables tumors and their margins clearly visualized, providing the potential for precisely imaging-guided phototherapy and treatment monitoring. To our knowledge, this is the first report that a small-molecule PS integrates both cancer PTT and PDT treatment by targeting mitochondria, significantly increasing the photosensitization. This work may also present a practicable strategy to develop small-molecule-based cancer theranostic agents for simultaneous cancer targeting, imaging, and therapy.

© 2017 Optical Society of America

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