Department of Dermatovenereology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, PR China; Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou 215006, PR China.
R&D Department of 3D printing, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, PR China.
J Control Release. 2024 Mar;367:470-485. doi: 10.1016/j.jconrel.2024.01.057. Epub 2024 Feb 2.
Despite the fact that immunotherapy has significantly improved the prognosis of melanoma patients, the non-response rate of monoimmunotherapy is considerably high due to insufficient tumor immunogenicity. Therefore, it is necessary to develop alternative methods of combination therapy with enhanced antitumor efficiency and less systemic toxicity. In this study, we reported a cancer cell membrane-coated zeolitic imidazole framework-8 (ZIF-8) encapsulating pyroptosis-inducer oxaliplatin (OXA) and immunomodulator imiquimod (R837) for chemoimmunotherapy. With the assistance of DNA methyltransferase inhibitor decitabine (DCT), upregulated Gasdermin E (GSDME) was cleaved by OXA-activated caspase-3, further inducing tumor cell pyroptosis, then localized antitumor immunity was enhanced by immune adjuvant R837, followed by triggering systemic antitumor immune responses. These results provided a proof-of-concept for the use of cell membrane-coated biomimetic nanoparticles as a promising drug carrier of combination therapy and a potential insight for pyroptosis-based melanoma chemo-immunotherapy.
尽管免疫疗法显著改善了黑色素瘤患者的预后，但由于肿瘤免疫原性不足，单免疫疗法的无反应率相当高。因此，有必要开发具有增强抗肿瘤效率和较低全身毒性的联合治疗替代方法。在这项研究中，我们报告了一种细胞膜包覆沸石咪唑骨架-8（ZIF-8）封装致炎细胞凋亡诱导剂奥沙利铂（OXA）和免疫调节剂咪喹莫特（R837）的用于化疗免疫治疗的方法。在 DNA 甲基转移酶抑制剂地西他滨（DCT）的辅助下，OXA 激活的 caspase-3 切割高表达的 Gasdermin E（GSDME），进一步诱导肿瘤细胞发生细胞焦亡，然后免疫佐剂 R837 增强局部抗肿瘤免疫，继而引发全身性抗肿瘤免疫反应。这些结果为细胞膜包覆仿生纳米颗粒作为联合治疗的有前途的药物载体提供了概念验证，并为基于细胞焦亡的黑色素瘤化疗免疫治疗提供了潜在的见解。
