Targeting and Energy-Depleting Biomimetic Nanoparticles for Enhancing Combined Chemo-Sonodynamic Therapy Against Esophageal Cancer

en This link goes to a English section zh This link goes to a Chinese section Esophageal cancer is the seventh leading cause of cancer death, and the energy depletion in cancer cells can be achieved through synergistic therapy. The integration of sonodynamic therapy and chemotherapy offers a promising comprehensive treatment strategy for esophageal cancer. However, a significant challenge lies in the efficient delivery of sound sensitizers and therapeutic agents. Herein, we present an energy-depleting biomimetic Zeolitic imidazolate framework-8 (ZIF-8) nanoparticle with high encapsulation efficiencies for the sonosensitizer Indocyanine green (ICG) and the chemotherapeutic agent Doxorubicin (DOX). By coating the nanoplatform with esophageal cancer cell membranes, we achieve enhanced homologous targeting to esophageal cancer cells, termed ICG/DOX/ZIF-8@M. In vitro and in vivo experiments demonstrated significant inhibition of tumor growth when treated with ICG/DOX/ZIF-8@M and ultrasonic stimulation. Single-cell RNA sequencing and mechanistic studies further elucidated the downregulation of energy metabolism-related pathways, including glutamine metabolism and glycolysis, which contribute to the enhanced efficacy of the combined therapy. Targeting and energy-depleting biomimetic ICG DOX/ZIF-8@M nanoparticles represent a promising strategy for esophageal cancer therapy. 摘要 en This link goes to a English section zh This link goes to a Chinese section 声动力疗法与化疗协同治疗策略可显著实现肿瘤能量耗竭, 抑制肿瘤生长, 是治疗食管鳞癌的一种前景广阔的策略。然而, 如何实现声敏剂和和化疗药物的高效递送仍然是一个重大挑战。为此, 我们开发了一种能量耗竭型仿生ZIF-8纳米颗粒(ICG/DOX/ZIF-8@M), 对声敏剂吲哚菁绿和化疗药物多柔比星具有极高的包封率, 采用食管癌细胞膜包覆可以通过同源靶向作用实现药物高效递送。体外和体内实验结果表明, ICG/DOX/ZIF-8@M联合超声处理显著抑制肿瘤生长。单细胞RNA测序与分子水平研究表明, ICG/DOX/ZIF-8@M显著下调谷氨酰胺代谢和糖酵解等能量代谢相关通路, 实现肿瘤能量耗竭。综上, 靶向能量耗竭型仿生ICG/DOX/ZIF-8@M纳米颗粒为食管癌治疗提供了一种富有前景的治疗策略。