文献名：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)

作者： Weihong Guo, Zhian Chen, Xiaoli Feng, Guodong Shen, Huilin Huang, Yanrui Liang, Bingxia Zhao, Guoxin Li, Yanfeng Hu

Department of General Surgery, Nanfang Hospital, Southern Medical University

摘要：

Background

Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while Pglycoprotein (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-OSAcould 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 Pgp, 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 (Scheme 1).

Conclusions

In conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy.

关键词：Graphene oxide (GO), drug resistance, P-glycoprotein (P-gp), chemo/photothermal (PTT)/photodynamic (PDT) therapy, mitochondrial respiratory chain