NO-dependent vasodilation and deep tumor penetration for cascade-amplified antitumor performance

被引：0

作者：

Xu, Qing ^{[1
]}

Chen, Gui ^{[1
]}

Chen, Guimei ^{[1
]}

Wu, Hualan ^{[3
]}

Yang, Yuanyuan ^{[1
]}

Mai, Ziyi ^{[1
]}

Sun, Rui ^{[1
]}

Luan, Ping ^{[4
]}

Guo, Chaowan ^{[5
]}

Yu, Meng ^{[1
]}

Peng, Zhenwei ^{[2
]}

Yu, Zhiqiang ^{[1
]}

机构：

[1] Guangdong Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou,510515, China

[2] Department of Radiation Oncology, Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou,510080, China

[3] The First Clinical Medical School, Southern Medical University, Guangzhou,510515, China

[4] Guangdong Second Provincial General Hospital & Health Science Center, Shenzhen University, Shenzhen,518060, China

[5] Guangdong Marubi Biotechnology Co., Ltd., No 92 Banhe Road, Huangpu District, Guangzhou,510700, China

来源：

Journal of Controlled Release | 2022年 / 347卷

基金：

中国国家自然科学基金;

关键词：

Blood vessels - Nitric oxide - Blood - Nitrogen - Unsaturated fatty acids;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Nonspecific biodistribution and poor permeability of conventional therapeutic agents in solid tumors severely compromised the antitumor efficacy. Herein, we report a cascade tumor therapeutic nanoplatform consisting of docosahexaenoic acid (DHA) and nicorandil (NI), namely DNP, to specifically produce cytotoxic agents in tumor cells as well as dilating blood vessels to increase the intratumoral oxidative stress levels. The DHA embedded in the membrane could generate reactive oxygen species (ROS) meanwhile NI produced nitric oxide (NO) in response to intracellular glutathione (GSH) in tumors. Notably, the two functional species could further react in situ to form a more tumoricidal reactive nitrogen species (RNS), causing selectively cascade amplification of antitumor performance. In addition, NO-induced vasodilation could consequently result in a series of functions, including hypoxia relief and deep tumor transportation. In general, we anticipate that the DNP could show great potential for tumor-specific treatment by selectively producing RNS precursors in response to the interior environment of tumor cells for hypoxia normalization and tumor inhibition. © 2022

引用

页码：389 / 399