School of Life Science, Beijing Institute of Technology, No.5 South Zhong Guan Cun Street, Beijing, 100081, China.
School of Materials Science and Engineering, Beijing Institute of Technology, China.
Angew Chem Int Ed Engl. 2021 Nov 22;60(48):25365-25371. doi: 10.1002/anie.202109258. Epub 2021 Oct 21.
Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5-aminolevulinate hydrochloride (HAL) and 3-bromopyruvic acid (3BP) into microparticles collected from X-ray-irradiated tumor cells (X-MP). After systemic administration, the developed HAL/3BP@X-MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co-localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes.
将光动力疗法（PDT）的基本要素定位于线粒体附近，可以克服活性氧（ROS）转移的严格时空限制，从而使 PDT 产生显著差异。然而，精确地将光敏剂（PS）和氧气积聚在线粒体中仍然具有挑战性。我们将盐酸 5-氨基酮戊酸己酯（HAL）和 3-溴丙酮酸（3BP）同时包封在 X 射线辐照肿瘤细胞收集的微颗粒中（X-MP）。经系统给药后，所开发的 HAL/3BP@X-MP 可以特异性地靶向和识别肿瘤细胞，其中 HAL 通过内在血红素生物合成途径诱导 PpIX 在线粒体中的有效积累。同时，3BP 通过抑制线粒体呼吸显著增加氧气供应。PpIX 和氧气的准确共定位和快速相遇产生足够的 ROS 直接破坏线粒体，从而显著改善 PDT 效果。
