期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 23, 页码 26808-26823出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c07494
关键词
high-intensity focused ultrasound; tumor hypoxic microenvironment; nitric oxide; reactive oxygen species; multidrug resistance
资金
- National Natural Science Foundation of China [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]
The combination of HIFU and chemotherapy has promising potential in treating solid tumors, but the hypoxic tumor microenvironment can impede clinical efficacy. This study developed nanoparticles capable of generating NO and ROS at the tumor site to relieve hypoxia, sensitizing solid tumors for chemotherapy and showing considerable potential in the management of hypoxic solid tumors.
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.
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