Cyclodextrin-Activated Porphyrin Photosensitization for Boosting Self-Cleavable Drug Release

作者：Mian Tang, Yanqiu Song, Yilin Lu, Ying‐Ming Zhang, Zhilin Yu, Xiufang Xu, Yu Liu · 发表于：Journal of Medicinal Chemistry · 年份：2022 · DOI：10.1021/acs.jmedchem.2c00105 · 被引用次数：32 · 研究领域：Nanoplatforms for cancer theranostics、Porphyrin and Phthalocyanine Chemistry、Photodynamic Therapy Research Studies

Supramolecular prodrugs that combine the merits of stimuli-responsiveness and targeting ability in a controllable manner have shown appealing prospects in disease diagnostics and therapeutics. Herein, we report that a new theranostic agent with the host–guest-binding-activated photosensitization has been fabricated by a binary supramolecular assembly consisting of the permethyl-β-cyclodextrin-grafted hyaluronic acid and a combretastatin A-4-appended porphyrin derivative. Illuminated by a red-light source, the production efficiency of singlet oxygen ( 1 O 2 ) pronouncedly increases by ∼60-fold once the porphyrin core is encapsulated by cyclodextrins. Consequently, the cell-selective fluorescence emission is dramatically enhanced, the microtubule-targeted drug is rapidly and completely released, and the 1 O 2 -involved combinational treatment is simultaneously achieved both in vitro and in vivo. To be envisaged, this complexation-boosted light-activatable photosensitizing prodrug delivery system with improved photophysical performance and remarkable phototheranostic outcomes will make a significant contribution to the creation of more advanced stimulus-based biomaterials.