Smart Tumor‐Cell‐Derived Microparticles Provide On‐Demand Photosensitizer Synthesis and Hypoxia Relief for Photodynamic Therapy

Abstract

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 recognizet umor cells,w here 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.

Hypoxia signaling in cancer: Implications for therapeutic interventions

“… 279 3‐Bromopyruvate inhibits hexokinase‐II activity, thereby inhibiting mitochondrial respiration and glycolysis and reducing mitochondrial oxygen consumption and ATP production. 280 Yu constructed a vesicular photodynamic therapy (PDT)‐specific PV‐TS nanoeconomizer, and an oxygen‐saver concept was proposed. PV‐TS can respond to tumor reduction conditions by releasing NO to inhibit cellular respiration, thereby reducing oxygen consumption and enabling biochemical redistribution of cellular oxygen resources to conserve oxygen.…”

Targeted implementation strategies of precise photodynamic therapy based on clinical and technical demands

“…62 In a study on the EV-modified PS, capsuled 5-HAL with tumor-derived EVs showed the property of specifically targeting and recognizing tumor cells. 63 However, it is worth noting that cancerous EVs might contain some oncogenes and lead to unintended consequences. Thus, circumspect research and evaluation are needed before the widespread application.…”

In Vivo Imaging for the Visualization of Extracellular Vesicle‐Based Tumor Therapy

“…[39][40] Zuo et al used tumor-cell released microvesicles to load drugs and achieved highly effective antitumor effects through the specific tumor-targeting ability of MVs. [41] Moreover, irradiated tumor-cell released MVs (RT-MVs) exhibit unique and broad antitumor abilities, and the yield of RT-MVs is significantly higher than that of unirradiated tumor cell-derived MVs. Wan found that, upon injection of RT-MVs into tumor-bearing mice, substantial amounts of RT-MVs were endocytosed by M2 tumor-associated macrophages (M2-TAMs), which were then polarized to anti-tumoral M1 macrophages.…”

“…Zuo et al. used tumor‐cell released microvesicles to load drugs and achieved highly effective antitumor effects through the specific tumor‐targeting ability of MVs [41] . Moreover, irradiated tumor‐cell released MVs (RT‐MVs) exhibit unique and broad antitumor abilities, and the yield of RT‐MVs is significantly higher than that of unirradiated tumor cell‐derived MVs.…”