线粒体在声动力疗法和抗肿瘤免疫中都至关重要。然而，如何精确地损伤线粒体，同时又防止线粒体自噬和免疫检查点抑制依然是一个巨大的挑战。在此，己酰5-氨基戊酸盐（HAL）和3-甲基腺嘌呤（3MA）被装载到肿瘤细胞源微粒（X-MP）中，可以将制备的HAL / 3MA @ X-MP有针对性地传递到肿瘤细胞中。HAL诱导有限的生物合成和PpIX在线粒体中的积累，导致超声辐照时局部产生活性氧（ROS），从而实现高效的线粒体损伤。同时，3MA不仅能抑制线粒体自噬，而且还能下调PD-L1表达，促进免疫原性细胞死亡（ICD）并阻止免疫检查点识别。精确线粒体损伤，线粒体自噬抑制和抗肿瘤免疫的智能协同作用，产生了强大的治疗效果，没有明显的副作用。

Mitochondria are crucial for both sonodynamic therapy and antitumor immunity. However, how to accurately damage mitochondria and meanwhile prevent the mitophagy and immune checkpoint inhibition is still a great challenge. Herein, hexyl 5-aminolevulinate hydrochloride (HAL) and 3-methyladenine (3MA) are loaded into the tumor cell-derived microparticle (X-MP), which can direct the target delivery of the prepared HAL/3MA@X-MP to the tumor cells. HAL induces the confined biosynthesis and accumulation of sonosensitizer PpIX in mitochondria, leading to the localized generation of reactive oxygen species (ROS) upon ultrasound irradiation and, thus, the efficient mitochondrial damage. Meanwhile, 3MA not only inhibits mitophagy but also down-regulates the PD-L1 expression, promoting the immunogenic cell death (ICD) while blocking the immune checkpoint recognition. The smart synergism of precise mitochondrial damage, mitophagy inhibition and antitumor immunity results in potent therapeutic efficacy without obvious side effects.