巨噬细胞
紫杉醇
癌症研究
医学
炎症
药物输送
癌症
三阴性乳腺癌
单核细胞
乳腺癌
体内
药理学
体外
免疫学
化学
生物
内科学
有机化学
生物技术
生物化学
作者
Yue Qiu,Kebai Ren,Wei Zhao,Qianwen Yu,Rong Guo,Jiao He,Ling Mei,Yayuan Liu,Jiajing Tang,Shanshan Xu,Jianping Li,Jiaojie Wei,Man Li,Zhirong Zhang,Qin He
标识
DOI:10.1016/j.jconrel.2020.11.039
摘要
Recurrence after tumor resection is mainly caused by post-operative inflammation and residual cancer cells, which is a serious obstacle to breast cancer treatment. Traditional nanoparticles rely primarily on the enhanced permeability and retention (EPR) effect in well-vascularized tumors. In this study, a macrophage-based carrier is designed to enhance the efficiency of targeting to recurrent tumors through a “dual-guide” strategy. After tumor resection, a burst of inflammatory factors occurs in the resection wound, which can recruit monocytes/macrophages rapidly. Combined with the tropism of monocyte chemoattractant protein, a large number of macrophage-mediated carriers will be recruited to surgical recurrence sites. Octaarginine (RRRRRRRR, R8)-modified liposomes in macrophages contain two agents with different pharmacological mechanisms, paclitaxel (PTX) and resveratrol (Res), which have enhanced therapeutic effects. In vitro study demonstrated that macrophage-mediated carriers approach 4 T1 cells through an inflammatory gradient and reach recurrence tumors through a “dual-guide” strategy. Then, membrane fusion and inflammation-triggered release deliver the drug into the recurrent tumor cells. In vivo experiments show that macrophage-based carriers exhibit effective tumor-targeting ability, especially in post-operation situations. More importantly, macrophage-mediated liposomes encapsulated with PTX and Res inhibit tumor recurrence in both ectopic and orthotopic 4 T1 post-operative recurrence models.
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