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

被引：231

作者：

Song, Qingle ^{[1
]}

Yin, Yijia ^{[1
]}

Shang, Lihuan ^{[1
]}

Wu, Tingting ^{[1
]}

Zhang, Dan ^{[1
]}

Kong, Miao ^{[1
]}

Zhao, Yongdan ^{[1
]}

He, Yangzhou ^{[1
]}

Tan, Songwei ^{[1
]}

Guo, Yuanyuan ^{[1
,2
]}

Zhang, Zhiping ^{[1
,3
,4
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Sch Pharm, Wuhan 430030, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol, Dept Pharm, Liyuan Hosp, Wuhan 430030, Hubei, Peoples R China

[3] Huazhong Univ Sci & Technol, Natl Engn Res Ctr Nanomed, Wuhan 430030, Hubei, Peoples R China

[4] Huazhong Univ Sci & Technol, Hubei Engn Res Ctr Novel Drug Delivery Syst, Wuhan 430030, Hubei, Peoples R China

来源：

NANO LETTERS | 2017年 / 17卷 / 10期

基金：

中国国家自然科学基金;

关键词：

Antitumor agents; chemo-immunotherapy; drug delivery; nanogel; tumor microenvironment; DRUG-DELIVERY SYSTEMS; BLOOD-CELL-MEMBRANE; POLYMERIC NANOPARTICLES; CO-DELIVERY; CONVENTIONAL CHEMOTHERAPY; BIOMEDICAL APPLICATIONS; CANCER-IMMUNOTHERAPY; ENHANCED SOLUBILITY; CHITOSAN; THERAPY;

D O I：

10.1021/acs.nanolett.7b03186

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A biomimetic nanogel with tumor microenvironment responsive property is developed for the combinatorial antitumor effects of chemotherapy and immunotherapy. Nanogels are formulated with hydroxypropyl-beta-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.

引用

页码：6366 / 6375

页数：10

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