Enzyme‐Directed and Organelle‐Specific Sphere‐to‐Fiber Nanotransformation Enhances Photodynamic Therapy in Cancer Cells

作者：Shenglong Gan, Yang Liu, Yiyuan Heng, Qingxin Chen, Dongqing Wang, Jie Zhang, Wenyu Wei, Zhiyang Liu, Demian I. Njoku, Jian Lin Chen, Yi Hu, Hongyan Sun · 发表于：Small Methods · 年份：2024 · DOI：10.1002/smtd.202301551 · 被引用次数：14 · 研究领域：Nanoplatforms for cancer theranostics、Porphyrin and Phthalocyanine Chemistry、Luminescence and Fluorescent Materials

Employing responsive nanoplatforms as carriers for photosensitizers represents an effective strategy to overcome the challenges associated with photodynamic therapy (PDT), including poor solubility, low bioavailability, and high systemic toxicity. Drawing inspiration from the morphology transitions in biological systems, a general approach to enhance PDT that utilizes enzyme-responsive nanoplatforms is developed. The transformation of phosphopeptide/photosensitizer co-assembled nanoparticles is first demonstrated into nanofibers when exposed to cytoplasmic enzyme alkaline phosphatase. This transition is primarily driven by alkaline phosphatase-induced changes of the nanoparticles in the hydrophilic and hydrophobic balance, and intermolecular electrostatic interactions within the nanoparticles. The resulting nanofibers exhibit improved ability of generating reactive oxygen species (ROS), intracellular accumulation, and retention in cancer cells. Furthermore, the enzyme-responsive nanoplatform is expanded to selectively target mitochondria by mitochondria-specific enzyme sirtuin 5 (SIRT5). Under the catalysis of SIRT5, the succinylated peptide/photosensitizer co-assembled nanoparticles can be transformed into nanofibers specifically within the mitochondria. The resulting nanofibers exhibit excellent capability of modulating mitochondrial activity, enhanced ROS formation, and significant anticancer efficacy via PDT. Consequently, the enzyme-instructed in situ fibrillar transform...