Hemin-lipid assembly as an artemisinin oral delivery system for enhanced cancer chemotherapy and immunotherapy.
Hemin-lipid assembly as an artemisinin oral delivery system for enhanced cancer chemotherapy and immunotherapy.
复制标题
DOI：
10.1039/d1nr01302e
复制
发表时间：
2021-08
期刊：
影响因子：
6.7
通讯作者：
Qing Wang;Naijie Wei;Jingru Guo;Kai Feng;Y. Wong;Jingwei Zhang;Jigang Wang;Xiaolian Sun
中科院分区：
文献类型：
--
作者：
Qing Wang;Naijie Wei;Jingru Guo;Kai Feng;Y. Wong;Jingwei Zhang;Jigang Wang;Xiaolian Sun
尽管青蒿素(Artemisin，ART)在肿瘤治疗中已显示出初步的前景，但其抑瘤效果较低，分布不佳，限制了其治疗效果。考虑到血红素在抗癌药物ART特异性杀寄生虫作用中的重要作用，我们设计了一种由氯化高铁血红素-脂质自组装而成的脂质体纳米结构，用于将抗癌药物ART和氯化高铁血红素共同输送到肿瘤治疗中。体外和体内实验均证实了氯化血红素和ART的协同化疗和免疫治疗作用。脂质体样结构在血液循环和胃肠道环境中相对稳定，但在肿瘤细胞环境中解离。叶酸(FA)的修饰不仅提高了它们在上皮细胞中的转运效率，而且增加了它们的肿瘤蓄积。在小鼠模型中，每隔一天口服FA-HEMEMEM-ART纳米粒(共5 mg·kg~(-1)ART)，并腹腔注射程序性死亡配体1抗体(APD-L1，共70μg/只)，30天内完全抑制MC38肿瘤。由于强烈的免疫记忆效应，治愈的小鼠在再次接种MC38细胞30天后仍然没有肿瘤。
Although artemisinin (ART) has shown initial promise in cancer therapy, its therapeutic efficacy is limited by its low tumor inhibitory efficacy and unfavorable distribution. Considering the important role of heme in the specific parasite-killing effect of ART, we designed a liposomal nanostructure self-assembled from hemin-lipid (Hemesome) to co-deliver ART and hemin for cancer therapy. The synergistic chemotherapeutic and immunotherapeutic effects of hemin and ART were demonstrated both in vitro and in vivo. The liposome-like structure was relatively stable in the blood circulation and gastrointestinal tract environment, but dissociated in the tumor cell environment. The folic acid (FA) modification not only increased their efficiency for transport across the epithelium, but also increased their tumor accumulation. In mouse models, following oral administration of FA-Hemesome-ART nanoparticles (5 mg kg-1 ART in total) every other day and intraperitoneal injection with a programmed death-ligand 1 antibody (aPD-L1, 70 μg per mouse in total), MC38 tumors were completely inhibited within 30 days. The cured mice remained tumor-free 30 days after rechallenging them with another inoculation of MC38 cells due to the strong immune memory effect.