医学
奥沙利铂
免疫原性细胞死亡
免疫疗法
肿瘤微环境
癌症研究
药理学
免疫系统
前药
结直肠癌
纳米医学
肿瘤缺氧
脂质体
癌症
免疫学
内科学
化学
放射治疗
材料科学
纳米技术
纳米颗粒
生物化学
作者
Song Li,Hao Yu,Chunjie Wang,Yikai Han,Yujie Zhu,Liangzhu Feng,Liyan Miao,Zhuang Liu
标识
DOI:10.1016/j.jconrel.2022.09.013
摘要
Tumor hypoxia is confirmed to be associated with the formation of tumor immunosuppression, a general feature of solid tumors, and thus attenuates the effectiveness of various cancer therapies in clinic. We herein develop a tumor microenvironment (TME) modulating liposomal nanomedicine by encapsulating metformin with amphiphilic oxaliplatin prodrug constructed liposomes to potentiate cancer immunotherapy. While metformin could regulate metabolisms of tumor cells to reduce their oxygen consumption and relieve tumor hypoxia, oxaliplatin is a chemotherapy drug that induces immunogenic cell death (ICD). The obtained met-oxa(IV)-liposome upon intravenous injection effectively attenuates tumor hypoxia and induce ICD of cancer cells, thereby collectively suppresses the growth of murine colorectal tumors by eliciting potent antitumor immunity and reversing the immunosuppressive TME. As the result, the treatment with met-oxa(IV)-liposome effectively potentiates the immune checkpoint blockade (ICB) therapy against murine colorectal tumors. This liposomal nanomedicine is highlighted to be a TME modulating liposomal nanomedicine with high potency in suppressing tumor growth, particularly promising in synergizing with ICB therapy by boosting antitumor immune responses.
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