Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 48, Pages 25365-25371Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202109258
Keywords
accurate delivery; biosynthesis; photodynamic therapy; relief hypoxia
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Funding
- National Natural Science Foundation of China [21904012, 21874011, 91859123, 32101140]
- National Science Fund for Distinguished Young Scholars [22025401]
- China Postdoctoral Science Foundation [2021TQ0037, 2021M690405, 2020M680396]
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The study encapsulated HAL and 3BP in microparticles collected from X-ray-irradiated tumor cells, allowing for specific targeting and recognition of tumor cells. This led to efficient accumulation of PpIX and increased oxygen supply, resulting in improved PDT outcomes by disrupting mitochondria with sufficient ROS.
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.
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