Ultrasound-responsive alkaline nanorobots for the treatment of lactic acidosis-mediated doxorubicin resistance. Issue 25 (23rd June 2020)

• Record Type: Journal Article
• Authors: Meng, Xia; Xu, Yurui; Lu, Qiangbing; Sun, Lei; An, Xueying; Zhang, Jikang; Chen, Jianmei; Gao, Ya; Zhang, Yu; Ning, Xinghai
• Is Part Of: Nanoscale. Volume 12:Issue 25(2020)
• Page Start: 13801
• Page End: 13810
• Publication Date: 2020-06-23
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d0nr03726e
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Lactic acidosis is one of the key characteristics of the tumor microenvironment (TME), and plays a critical role in therapy resistance, making it an attractive target for enhancing anticancer treatment. Abstract : Lactic acidosis is one of the key characteristics of the tumor microenvironment (TME), and plays a critical role in therapy resistance, making it an attractive target for enhancing anticancer treatment. However, no effective systems exhibit the ability to selectively neutralize tumor lactic acidosis in a controlled manner. Here, we have developed novel ultrasound-responsive alkaline nanorobots (AN-DSP), composed of PLGA nanoparticles containing doxorubicin (DOX), sodium carbonate (Na2 CO3 ) and perfluorocarbon (PFC), for recovering from lactic acidosis-mediated drug resistance. AN-DSP exhibit sensitive response to ultrasound stimulation, and rapidly release Na2 CO3 to neutralize lactic acidosis, consequently enhancing DOX susceptibility in vitro and in vivo . Particularly, our nanorobots autonomously accumulate in tumors by an enhanced permeability and retention effect, and can specifically disrupt the tumor acidic microenvironment in response to external ultrasonic powering, resulting in the inhibition of tumor growth with minimal adverse effects. Therefore, AN-DSP represent a promising approach for selectively overcoming tumor lactic acidosis induced therapeutic resistance.