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)

Abstract

BackgroundPaclitaxel (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. ResultsIn 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 (Scheme 1). ConclusionsIn conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy.

Photodynamic Therapy—An Up-to-Date Review

“…PDT was reported effective in the treatment of gastrointestinal tract malignancies [125], being used for the remedy of esophageal [11,126,127], gastric [59,[128][129][130], liver [131,132], pancreatic [133][134][135], and colorectal [136][137][138] cancers. The main advantages of using PDT for these types of cancer are the less-invasive nature compared to surgery and wider indication than endoscopic resection.…”

Curcumin/L‐OHP co‐loaded HAP for cGAS‐STING pathway activation to enhance the natural immune response in colorectal cancer

“…Nanotechnology-based drug-delivery systems have emerged as promising alternatives to conventional chemotherapy strategies due to their efficient drug-delivery properties. 30 We expected that HAP would enable efficient intracellular delivery of curcumin and L-OHP to CRC cells. Rhodamine B (red) was used to label the Cur/L-OHP@HAP NPs, and CLSM and flow cytometry were used to detect Cur/L-OHP @HAP NPs uptake in CT26 cells by monitoring the fluorescence intensity of rhodamine B.…”