Selective Intratumoral Drug Release and Simultaneous Inhibition of Oxidative Stress by a Highly Reductive Nanosystem and Its Application as an Anti-tumor Agent

被引：10

作者：

Zhu, Chunqi ^{[1
]}

Luo, Lihua ^{[1
]}

Jiang, Xindong ^{[1
]}

Jiang, Mengshi ^{[1
]}

Luo, Zhenyu ^{[1
]}

Li, Xiang ^{[1
]}

Qiu, Weigen ^{[1
]}

Jin, Zhaolei ^{[1
]}

Shen, Tianxiang ^{[1
]}

Li, Chunlong ^{[1
]}

Li, Qingpo ^{[1
]}

Qiu, Yunqing ^{[2
]}

You, Jian ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, State Key Lab Diag & Treatment Infect Dis, Collaborat Innovat Ctr Diag & Treatment Infect Di, Affiliated Hosp 1, 79 Qingchun Rd, Hangzhou 31003, Zhejiang, Peoples R China

来源：

THERANOSTICS | 2020年 / 10卷 / 03期

基金：

国家重点研发计划;

关键词：

Oxidative Stress; Docetaxel; Reductive nanosystem; Selective release; Systemic toxicity; PEROXYL RADICAL SCAVENGER; BREAST-CANCER CELLS; VITAMIN-E; TUMOR AUTOPHAGY; ALPHA-TEA; DOCETAXEL; ROS; DOXORUBICIN; PACLITAXEL; APOPTOSIS;

D O I：

10.7150/thno.38627

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Excessive oxidative stress is always associated with the serious side effects of chemotherapy. In the current study, we developed a vitamin E based strongly reductive nanosystem to increase the loading efficiency of docetaxel (DTX, DTX-VNS), reduce its side toxicity and enhance the antitumor effect. Methods: We used Forster Resonance Energy Transfer (FRET) to reveal the in vivo and in vitro fate of DTX-VNS over time. All FRET images were observed using the Maestro imaging system (CRI, Inc., Woburn, MA) and Fluo-View software (Olympus LX83-FV3000). Results: Through FRET analyzing, we found that our nanosystem showed a selective rapider release of drugs in tumors compared to normal organs due to the higher levels of ROS in tumor cells than normal cells, and the accumulation of DTX at tumor sites in the DTX-VNS group was also notably more than that in the Taxotere group after 24 h injection. Meanwhile, DTX-VNS had a prominently stronger anti-tumor effect in various models than Taxotere, and had a synergistic effect of immunotherapy. Conclusions: Our work presented a useful reference for clinical exploration of the in vivo behavior of nanocarriers (DTX-VNS), inhibition oxidative stress and selective release of drugs at tumor sites, thus reducing the side effects and enhancing the anti-tumor effects.

引用

页码：1166 / 1180

页数：15

共 51 条

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