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<p>Exosomes have emerged as promising drug delivery carriers for targeting tumorigenesis, metastasis, and multidrug resistance, owing to their inherent therapeutic capabilities in regulating intercellular communications. Conventional exosome engineering involves sequential isolation and therapeutic cargo loading procedures, which complicate their functionalization and applications. In this study, we present an <i>in situ</i> engineering strategy of a photosensitizer (PS)-exosome nanoplatform for activating multiple programmed cell death (PCD) pathways in recipient cancer cells. The constructed PS DPNVP exhibits aggregation-induced emission characteristics and possesses prominent type I and II reactive oxygen species (ROS) generation capacity under white light irradiation. The suitable lipocationic nature enables DPNVP to precisely anchor onto plasma membranes. Upon light irradiation, lethal ROS generated by DPNVP compromise the integrity of the plasma membrane, trigger pyroptosis and apoptosis, and eventually lead to immunogenic cell death. More importantly, DPNVP specifically labels exosomes during their secretion from originating cells. These <i>in-situ</i> engineered PS-exosome nanocomplexes can be effectively internalized by recipient cancer cells, activating concurrent pyroptosis and apoptosis in recipient cancer cells through potent photodynamic therapy.</p>

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In-situ engineered photosensitizer-exosome nanoplatform activates pyroptosis and apoptosis in recipient cells

  • 期刊论文

  • 发表日期：

    2025年10月17日

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  • Zhedong Ma,
  • Lijin Yang,
  • Jia Jia,
  • Yingying Ren,
  • Yun He,
  • Nan Li,
  • Na Zhao

摘要

Exosomes have emerged as promising drug delivery carriers for targeting tumorigenesis, metastasis, and multidrug resistance, owing to their inherent therapeutic capabilities in regulating intercellular communications. Conventional exosome engineering involves sequential isolation and therapeutic cargo loading procedures, which complicate their functionalization and applications. In this study, we present an in situ engineering strategy of a photosensitizer (PS)-exosome nanoplatform for activating multiple programmed cell death (PCD) pathways in recipient cancer cells. The constructed PS DPNVP exhibits aggregation-induced emission characteristics and possesses prominent type I and II reactive oxygen species (ROS) generation capacity under white light irradiation. The suitable lipocationic nature enables DPNVP to precisely anchor onto plasma membranes. Upon light irradiation, lethal ROS generated by DPNVP compromise the integrity of the plasma membrane, trigger pyroptosis and apoptosis, and eventually lead to immunogenic cell death. More importantly, DPNVP specifically labels exosomes during their secretion from originating cells. These in-situ engineered PS-exosome nanocomplexes can be effectively internalized by recipient cancer cells, activating concurrent pyroptosis and apoptosis in recipient cancer cells through potent photodynamic therapy.