Self-Amplification of Tumor Oxidative Stress with Degradable Metallic Complexes for Synergistic Cascade Tumor Therapy

被引：210

作者：

Chen, Gui ^{[1
]}

Yang, Yuanyuan ^{[1
]}

Xu, Qing ^{[1
]}

Ling, Mingjian ^{[2
]}

Lin, Huimin ^{[1
]}

Ma, Wen ^{[1
]}

Sun, Rui ^{[1
]}

Xu, Yuchun ^{[1
]}

Liu, Xiqiang ^{[2
]}

Li, Nan ^{[3
]}

Yu, Zhiqiang ^{[1
]}

Yu, Meng ^{[1
]}

机构：

[1] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China

[2] Southern Med Univ, Nanfang Hosp, Dept Oral & Maxillofacial Surg, Guangzhou 510515, Peoples R China

[3] Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin Key Lab Drug Delivery & High Efficiency, Tianjin 300072, Peoples R China

来源：

NANO LETTERS | 2020年 / 20卷 / 11期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

metallic complex; reactive oxygen species; Fenton reaction; tumor redox microenvironment; ferroptosis;

D O I：

10.1021/acs.nanolett.0c03127

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The ferroptosis effect has been illuminated with a clear Fenton reaction mechanism that converts endogenous hydrogen peroxide (H2O2) into highly oxidative hydroxyl radicals (center dot OH) in ROS-amplified tumor therapy. This ferroptosis-related oxidation effect was then further enhanced by the enzyme-like roles of cisplatin (CDDP). This CDDP-induced apoptosis was promoted in reverse by ferroptosis via the depletion of glutathione (GSH) and prevention of DNA damage repair. Here, we have developed degradable metallic complexes (PtH@FeP) containing an Fe(III)-polydopamine (FeP) core and HA-cross-linked CDDP (PtH) shell, exaggerating in situ toxic ROS production via the synergistic effect of CDDP and Fe(III). Taken together, the rationally designed PtH@FeP provided a new strategy for self-amplified synergistic chemotherapy/ferroptosis/photothermal therapy (PTT) antitumor effects with a reduced dosage that facilitates clinical safety.

引用

页码：8141 / 8150

页数：10

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