Nanoenabled Tumor Energy Metabolism Disorder via Sonodynamic Therapy for Multidrug Resistance Reversal and Metastasis Inhibition

作者全名："Guo, Xun; Tu, Peng; Zhu, Leilei; Cheng, Chen; Jiang, Weixi; Du, Chier; Wang, Xiaoting; Qiu, Xiaoling; Luo, Yuanli; Wan, Li; Tang, Rui; Ran, Haitao; Wang, Zhigang; Ren, Jianli"

作者地址："[Guo, Xun; Tu, Peng; Zhu, Leilei; Cheng, Chen; Jiang, Weixi; Du, Chier; Wang, Xiaoting; Qiu, Xiaoling; Luo, Yuanli; Wan, Li; Tang, Rui; Ran, Haitao; Wang, Zhigang; Ren, Jianli] Chongqing Med Univ, Dept Ultrasound, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Guo, Xun; Tu, Peng; Zhu, Leilei; Cheng, Chen; Jiang, Weixi; Du, Chier; Wang, Xiaoting; Qiu, Xiaoling; Luo, Yuanli; Wan, Li; Tang, Rui; Ran, Haitao; Wang, Zhigang; Ren, Jianli] Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Zhu, Leilei] Chongqing Gen Hosp, Dept Ultrasound, Chongqing 401147, Peoples R China; [Cheng, Chen] Chongqing Med Univ, Bishan Hosp Chongqing, Dept Ultrasound, Chongqing 402760, Peoples R China; [Qiu, Xiaoling] Chongqing Med Univ, Dept Intens Care Unit, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Wan, Li] Chongqing Med Univ, Hlth Management Ctr, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Wan, Li] Chongqing Med Univ, Phys Examinat Ctr, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："Ren, JL (通讯作者)，Chongqing Med Univ, Dept Ultrasound, Affiliated Hosp 2, Chongqing 400010, Peoples R China.; Ren, JL (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：ACS APPLIED MATERIALS & INTERFACES

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000917983400001

JCR分区：Q1

影响因子：8.3

年份：2023

卷号：15

期号：1

开始页：309

结束页：326

文献类型：Article

关键词：multidrug resistance; tumor energy metabolism; sonodynamic therapy; mitochondrial apoptosis; immunogenic cell death

摘要："Cancer multidrug resistance (MDR) is an important reason that results in chemotherapy failure. As a main mechanism of MDR, overexpressed P-glycoprotein (P-gp) utilizes adenosine triphosphate (ATP) to actively pump chemotherapy drugs out of cells. In addition, metabolic reprogramming of drug-resistant tumor cells (DRTCs) exacerbates the specific hypoxic microenvironment and promotes tumor metastasis and recurrence. Therefore, we propose a novel sonodynamic therapy (SDT) paradigm to induce energy metabolism disorder and drug resistance change of DRTCs. A US-controlled ""Nanoenabled Energy Metabolism Jammer"" (TL@HPN) is designed using perfluoropentane (PFP) adsorbing oxygen in the core, and a targeting peptide (CGNKRTR) is attached to the liposome as the delivery carrier shell to incorporate hematoporphyrin monomethyl ether (HMME) and paclitaxel (PTX). The TL@HPN with ultrasonic/photoacoustic imaging (PAI/USI) precisely controlled the release of drugs and oxygen after being triggered by ultrasound (US), which attenuated the hypoxic microenvironment. SDT boosted the reactive oxygen species (ROS) content in tumor tissues, preferentially inducing mitochondrial apoptosis and maximizing immunogenic cell death (ICD). Persistently elevated oxidative stress levels inhibited ATP production and downregulated P-gp expression by disrupting the redox balance and electron transfer of the respiratory chain. We varied the effect of TL@HPN combined with PD-1/PD-L1 to activate autoimmunity and inhibit tumor metastasis, providing a practical strategy for expanding the use of SDT-mediated tumor energy metabolism."

基金机构："National Natural Science Foundation of China [82171946, 81873901]; Basic Research and Frontier Exploration Key Project of Chongqing Science and Technology Commission [cstc2019jcyj- zdxmX0020]; High-level Medical Reserved Personnel Training Project of Chongqing; CQMU Program for Youth Innovation in Future Medicine [W0026]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [KR2019G001]; Chongqing Science and Health Joint Medical Research Project-Young and Middle-aged High-level Talent Project [2020GDRC011]; Chongqing Municipal Health Commission [2021MSXM129]; Chongqing Science and Technology Bureau [2021MSXM129]; Municipal Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0569]"

基金资助正文："The authors are sincerely grateful for the financial support from the National Natural Science Foundation of China (Grant Nos. 82171946 and 81873901) , the Basic Research and Frontier Exploration Key Project of Chongqing Science and Technology Commission (Grant No. cstc2019jcyj- zdxmX0020) , the High-level Medical Reserved Personnel Training Project of Chongqing, the CQMU Program for Youth Innovation in Future Medicine (W0026) , the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (KR2019G001) , and Chongq- ing Science and Health Joint Medical Research Project-Young and Middle-aged High-level Talent Project (2020GDRC011) , the Joint Medical Research Program of Chongqing Municipal Health Commission and Chongqing Science and Technology Bureau (Grant No. 2021MSXM129) , and the Municipal Natural Science Foundation of Chongqing (Grant No. cstc2020jcyj-msxmX0569) ."