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

• DOI: 10.1021/acsami.2c16278
• Publication Date: 2022-12-28T15:20:50Z
• Authors: Xun Guo; Peng Tu; Leilei Zhu; Chen Cheng; Weixi Jiang; Chier Du; Xiaoting Wang; Xiaoling Qiu; Yuanli Luo; Li Wan; Rui Tang; Haitao Ran; Zhigang Wang; Jianli Ren
• Keywords: Sonodynamic therapy

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