文獻(xiàn)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.
關(guān)鍵詞:Graphene oxide (GO), drug resistance, P-glycoprotein (P-gp), chemo/photothermal (PTT)/photodynamic (PDT) therapy, mitochondrial respiratory chain
|