Glutathione-Activated NO-/ROS-Generation Nanoparticles to Modulate the Tumor Hypoxic Microenvironment for Enhancing the Effect of HIFU-Combined Chemotherapy

作者全名："Li, Qianyan; Zhang, Jingni; Li, Jingnan; Ye, Hemin; Li, Meixuan; Hou, Wei; Li, Huanan; Wang, Zhibiao"

作者地址："[Li, Qianyan; Zhang, Jingni; Li, Jingnan; Ye, Hemin; Li, Meixuan; Hou, Wei; Li, Huanan; Wang, Zhibiao] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China"

通信作者："Li, HA; Wang, ZBA (corresponding author), Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China."

来源：ACS APPLIED MATERIALS & INTERFACES

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000664289800015

JCR分区：Q1

影响因子：9.5

年份：2021

卷号：13

期号：23

开始页：26808

结束页：26823

文献类型：Article

关键词：high-intensity focused ultrasound; tumor hypoxic microenvironment; nitric oxide; reactive oxygen species; multidrug resistance

摘要："The combination of high-intensity focused ultrasound (HIFU) and chemotherapy has promising potential in the synergistic treatment of various types of solid tumors. However, the clinical efficacy of HIFU in combination chemotherapy is often impeded by the preexisting hypoxia tumor microenvironment-induced multidrug resistance (MDR). Therefore, it is imperative for HIFU combined with chemotherapy to overcome MDR by improving the tumor hypoxic microenvironment. Hence, we developed highly stable nanoparticles (P@BDOX/beta-lapachone-NO-NPs) with intracellular nitric oxide (NO)- and reactive oxygen species (ROS)-generating capabilities at the tumor site to relieve the hypoxic tumor microenvironment in solid tumors. Doxorubicin prodrug (boronate-DOX, BDOX) and beta-lapachone were concurrently loaded onto actively targeted pH (low) insertion peptides (pHLIPs)-poly(ethylene glycol) and nitrated gluconic acid copolymers. Our results showed that the ability of P@BDOX/beta-lapachone-NO-NPs to generate NO and ROS simultaneously is vital for the sensitization of hypoxic solid tumors for chemotherapy, as evidenced by the suppression of tumor cells and tissues (in vitro and in the nude mice model). Thus, this combined therapy holds considerable potential in the management of hypoxic solid tumors."

基金机构：National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82001851]; Chongqing Research Program of Basic Research and Frontier Technology [cstc2019jcyj-msxmX0334]; Yuzhong District Research Program of Basic Research and Frontier Technology of Chongqing [20180110]

基金资助正文："This project was financially supported by the National Natural Science Foundation of China (no. 82001851 to H.L.), the Chongqing Research Program of Basic Research and Frontier Technology (no. cstc2019jcyj-msxmX0334 to H.L.), and the Yuzhong District Research Program of Basic Research and Frontier Technology of Chongqing (no. 20180110 to H.L.)"