Hu Mei, Zhang Jiao, Kong Li, Yu Yulin, Hu Qian, Yang Ting, Wang Yi, Tu Kun, Qiao Qi, Qin Xianya, Zhang Zhiping
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430030, China.
ACS Nano. 2021 Feb 23;15(2):3123-3138. doi: 10.1021/acsnano.0c09681. Epub 2021 Jan 20.
Exploring a rational delivery system of integrating chemotherapy with immunotherapy to broaden benefits of cancer immunochemotherapy is still under challenge. Herein, we developed doxorubicin (DOX)-loaded biomimetic hybrid nanovesicles (DOX@LINV) fusing artificial liposomes (LIPs) with tumor-derived nanovesicles (TNVs) for combinational immunochemotherapy. DOX@LINV with a homologous targeting ability could deliver DOX to tumor tissue and elicit an effective immunogenic cell death response to improve the immunogenicity of a tumor. Meanwhile, the preserved tumor antigens and endogenous danger signals in DOX@LINV activated dendritic cells and induced a subsequent antigen-specific T cell immune response. DOX@LINV displayed a specific antitumor effect on murine melanoma, Lewis lung cancer, and 4T1 breast cancer based on the infiltration of effector immune cells and improvement of the immunosuppressive tumor microenvironment. Furthermore, the combination of DOX@LINV with immune checkpoint inhibitor amplified antitumor efficacy with 33.3% of the mice being tumor-free. Therefore, the hybrid LINV is a promising drug delivery platform with a boosted antitumor immune response for effective immunochemotherapy.
探索一种将化疗与免疫疗法相结合的合理给药系统以扩大癌症免疫化疗的益处仍面临挑战。在此,我们开发了一种载有多柔比星(DOX)的仿生杂交纳米囊泡(DOX@LINV),它将人工脂质体(LIPs)与肿瘤衍生纳米囊泡(TNVs)融合用于联合免疫化疗。具有同源靶向能力的DOX@LINV可将DOX递送至肿瘤组织,并引发有效的免疫原性细胞死亡反应以提高肿瘤的免疫原性。同时,DOX@LINV中保留的肿瘤抗原和内源性危险信号激活树突状细胞并诱导随后的抗原特异性T细胞免疫反应。基于效应免疫细胞的浸润和免疫抑制性肿瘤微环境的改善,DOX@LINV对小鼠黑色素瘤、Lewis肺癌和4T1乳腺癌显示出特异性抗肿瘤作用。此外,DOX@LINV与免疫检查点抑制剂联合使用可增强抗肿瘤疗效,33.3%的小鼠无肿瘤。因此,杂交LINV是一种有前景的药物递送平台,具有增强的抗肿瘤免疫反应以实现有效的免疫化疗。