| Title | Biomimetic Nanovesicle with Mitochondria-Synthesized Sonosensitizer and Mitophagy Inhibition for Cancer Sono- Immunotherapy |
| Authors | Zuo, Liping Nie, Weidong Yu, Songmao Zhuang, Wan-Ru Liang, Chao Li, Sucheng Shi, Danshu Wu, Guanghao Sui, Xin Li, Yongheng Xie, Hai-Yan |
| Affiliation | Peking Univ, Chem Biol Ctr, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China Peking Univ Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Dept Radiat Oncol, Beijing 100142, Peoples R China Beijing Inst Technol, Sch Life Sci, Beijing 100081, Peoples R China Shimadzu China Co LTD, Beijing Branch, Beijing 100020, Peoples R China |
| Keywords | PD-L1 |
| Issue Date | Mar-2023 |
| Publisher | NANO LETTERS |
| Abstract | 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 sonosensi-tizer 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. |
| URI | http://hdl.handle.net/20.500.11897/674977 |
| ISSN | 1530-6984 |
| DOI | 10.1021/acs.nanolett.3c00383 |
| Indexed | EI SCI(E) |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 北京肿瘤医院 |
