Graphene oxide (GO)-based nanosheets with combined chemo/photothermal/photodynamic therapy to overcome gastric cancer (GC) paclitaxel resistance by reducing mitochondria-derived adenosine-triphosphate (ATP)

Journal of Nanobiotechnology

Guodong Shen¹  Yanfeng Hu¹  Guoxin Li¹  Weihong Guo¹  Yanrui Liang¹  Huilin Huang¹  Zhian Chen¹  Bingxia Zhao²  Xiaoli Feng³ 

[1] Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University;Guangdong Provincial Key Laboratory of Cancer Immunotherapy, Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University;Guangdong Provincial Stomatology Hospital, Southern Medical University;

关键词: Graphene oxide (GO);    Drug resistance;    P-glycoprotein (P-gp);    Chemo/photothermal (PTT)/photodynamic (PDT) therapy;    Mitochondrial respiratory chain;   

DOI  :  10.1186/s12951-021-00874-9

来源: DOAJ

【 摘 要 】

Abstract Background Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while P-glycoprotein (P-gp) could lead to drug resistance by pumping PTX out of GC cells. Consequently, it might be a hopeful way to combat drug resistance by inhibiting the out-pumping function of P-gp. Results In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)-modified and oxidized sodium alginate (OSA)-functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)-irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for P-gp, and effectively inhibit P-gp’s efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity. Conclusions In conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy. Graphic Abstract

【 授权许可】

Unknown