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 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...

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Main Authors: Weihong Guo, Zhian Chen, Xiaoli Feng, Guodong Shen, Huilin Huang, Yanrui Liang, Bingxia Zhao, Guoxin Li, Yanfeng Hu
Format: Article
Language:English
Published: BMC 2021-05-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-021-00874-9
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author Weihong Guo
Zhian Chen
Xiaoli Feng
Guodong Shen
Huilin Huang
Yanrui Liang
Bingxia Zhao
Guoxin Li
Yanfeng Hu
author_facet Weihong Guo
Zhian Chen
Xiaoli Feng
Guodong Shen
Huilin Huang
Yanrui Liang
Bingxia Zhao
Guoxin Li
Yanfeng Hu
author_sort Weihong Guo
collection DOAJ
description 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
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spelling doaj.art-d2e26533919e4b108af400c56f13e8e52022-12-22T04:31:28ZengBMCJournal of Nanobiotechnology1477-31552021-05-0119111910.1186/s12951-021-00874-9Graphene oxide (GO)-based nanosheets with combined chemo/photothermal/photodynamic therapy to overcome gastric cancer (GC) paclitaxel resistance by reducing mitochondria-derived adenosine-triphosphate (ATP)Weihong Guo0Zhian Chen1Xiaoli Feng2Guodong Shen3Huilin Huang4Yanrui Liang5Bingxia Zhao6Guoxin Li7Yanfeng Hu8Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Stomatology Hospital, Southern Medical UniversityDepartment of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Cancer Immunotherapy, Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical UniversityDepartment of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical UniversityDepartment of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12951-021-00874-9Graphene oxide (GO)Drug resistanceP-glycoprotein (P-gp)Chemo/photothermal (PTT)/photodynamic (PDT) therapyMitochondrial respiratory chain
spellingShingle Weihong Guo
Zhian Chen
Xiaoli Feng
Guodong Shen
Huilin Huang
Yanrui Liang
Bingxia Zhao
Guoxin Li
Yanfeng Hu
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
Graphene oxide (GO)
Drug resistance
P-glycoprotein (P-gp)
Chemo/photothermal (PTT)/photodynamic (PDT) therapy
Mitochondrial respiratory chain
title 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)
title_full 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)
title_fullStr 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)
title_full_unstemmed 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)
title_short 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)
title_sort 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
topic Graphene oxide (GO)
Drug resistance
P-glycoprotein (P-gp)
Chemo/photothermal (PTT)/photodynamic (PDT) therapy
Mitochondrial respiratory chain
url https://doi.org/10.1186/s12951-021-00874-9
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