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).
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).
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DOI：
10.1186/s12951-021-00874-9
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发表时间：
2021-05-19
影响因子：
10.2
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Guo W;Chen Z;Feng X;Shen G;Huang H;Liang Y;Zhao B;Li G;Hu Y
紫杉醇（PTX）是治疗胃癌的一线药物，而P-糖蛋白（P-gp）可将PTX泵出胃癌细胞，导致胃癌耐药。因此，通过抑制P-gp的外泵功能来对抗耐药可能是一条有希望的途径。在这项研究中，我们开发了一种药物递送系统，将PTX结合到聚乙二醇（PEG）修饰和氧化海藻酸钠（OSA）功能化的氧化石墨烯（GO）纳米片（NS）上，称为PTX@GO-PEG-OSA。由于PTX@GO-PEG-OSA具有pH/温度敏感性释药特性，与游离PTX相比，PTX@GO-PEG-OSA对GC具有更明显的抗肿瘤作用。PTX@GO-PEG-OSA在近红外（NIR）照射下可产生过量的活性氧（ROS），攻击线粒体呼吸链复合酶，减少P-gp对ATP的补充，有效抑制P-gp的外排泵功能。由此可见，PTX@GO-PEG-OSA对PTX耐药的GC取得了更好的治疗效果，且无明显毒性。总之，PTX@GO-PEG-OSA可以作为逆转PTX耐药性的理想策略，与化学/光热/光动力疗法相结合。在线版本包含补充材料，可通过10.1186/s12951-021-00874-9获得。
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. 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. In conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX’s resistance, combined with chemo/photothermal/photodynamic therapy. The online version contains supplementary material available at 10.1186/s12951-021-00874-9.
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