Weihong Guo1, Zhian Chen2, Xiaoli Feng3, Guodong Shen2, Huilin Huang2, Yanrui Liang2, Bingxia Zhao4, Guoxin Li5, Yanfeng Hu6. 1. Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. drguowh@163.com. 2. Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 3. Guangdong Provincial Stomatology Hospital, Southern Medical University, Guangzhou, 510000, China. 4. 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, Guangzhou, 510515, PR China. bingxiaz@gmail.com. 5. Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. gzliguoxin@163.com. 6. Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. banby@smu.edu.cn.
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.
BACKGROUND:Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), whileP-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.
Authors: Kathleen A Cronin; Andrew J Lake; Susan Scott; Recinda L Sherman; Anne-Michelle Noone; Nadia Howlader; S Jane Henley; Robert N Anderson; Albert U Firth; Jiemin Ma; Betsy A Kohler; Ahmedin Jemal Journal: Cancer Date: 2018-05-22 Impact factor: 6.860
Authors: Bofang Wang; Yunpeng Wang; Tao Zhang; Lei Gao; Lin Xiang; Ewetse Paul Maswikiti; Na Wang; Yang Yu; Chenhui Ma; Huanhuan Ma; Hao Chen Journal: Transl Cancer Res Date: 2022-07 Impact factor: 0.496