State Key Laboratory of Virology, Department of Biochemistry and Molecular Biology, Hubei Key Laboratory of Cell Homeostasis, College of Life Science, Wuhan University, Wuhan, China.
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, China.
J Cell Physiol. 2020 May;235(5):4814-4823. doi: 10.1002/jcp.29358. Epub 2019 Oct 29.
CD8 T cells play a vital role in cancer immunotherapy and can be shaped by metabolism. Avasimibe is an acyl coenzyme A-cholesterol acyltransferase (ACAT) inhibitor, which has been clinically verified safe in other phase Ⅲ clinical trials. It can potentiate the killing function of CD8 T cells by modulating cholesterol metabolism. Doxorubicin (DOX) is an anticancer drug widely used in many cancers to induce tumor cell apoptosis. Unfortunately, DOX also can induce toxic and side effects in many organs, compromising its usage and efficacy. Herein, we report the combinational usage of avasimibe and a safe pH sensitive nano-drug delivery system composing of DOX and metal-organic frameworks nanoparticles (MNPs). Our findings demonstrated that DOX-MNPs treatment inhibited tumor growth with good safety profile and avasimibe treatment combined DOX-MNPs treatment exhibited a better efficacy than monotherapies in 4T1 breast cancer therapy.
CD8 T 细胞在癌症免疫治疗中起着至关重要的作用，其功能可以通过代谢来调节。阿伐麦布是一种酰基辅酶 A-胆固醇酰基转移酶（ACAT）抑制剂，在其他 III 期临床试验中已被临床证实安全。它可以通过调节胆固醇代谢来增强 CD8 T 细胞的杀伤功能。多柔比星（DOX）是一种广泛用于多种癌症的抗癌药物，可诱导肿瘤细胞凋亡。然而，DOX 也会在许多器官中引起毒性和副作用，从而限制了其使用和疗效。在此，我们报告了阿伐麦布与由 DOX 和金属有机框架纳米粒子（MNPs）组成的安全 pH 敏感纳米药物递送系统的联合使用。我们的研究结果表明，DOX-MNPs 治疗具有良好的安全性，抑制肿瘤生长，而阿伐麦布联合 DOX-MNPs 治疗在 4T1 乳腺癌治疗中比单药治疗具有更好的疗效。
