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Tumor Microenvironment Responsive Nanogel for the Combinatorial Antitumor Effect of Chemotherapy and Immunotherapy

Qingle SongTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaYijia YinTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaLihuan ShangTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaTingting WuTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaDan ZhangTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaMiao KongTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaYongdan ZhaoTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaYangzhou HeTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaSongwei TanTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaYuanyuan GuoTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, ChinaZhiping ZhangTongji School of Pharmacy, ‡Department of Pharmacy, Liyuan Hospital, §National Engineering Research Center for Nanomedicine, ∥Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, China
2017en
ABI

Аннотация

A biomimetic nanogel with tumor microenvironment responsive property is developed for the combinatorial antitumor effects of chemotherapy and immunotherapy. Nanogels are formulated with hydroxypropyl-β-cyclodextrin acrylate and two opposite charged chitosan derivatives for entrapping anticancer drug paclitaxel and precisely controlling the pH responsive capability, respectively. The nanogel supported erythrocyte membrane can achieve "nanosponge" property for delivering immunotherapeutic agent interleukin-2 without reducing the bioactivity. By responsively releasing drugs in tumor microenvironment, the nanogels significantly enhanced antitumor activity with improved drug penetration, induction of calreticulin exposure, and increased antitumor immunity. The tumor microenvironment is remodeled by the combination of these drugs in low dosage, as evidenced by the promoted infiltration of immune effector cells and reduction of immunosuppressive factors.

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