摘要
目的构建载顺铂(CDDP)并经二氧化锰(MnO2)修饰的纳米氧化石墨烯(NGO)递药系统CDDP/NGO@MH,并研究其对于逆转谷胱甘肽(GSH)介导的CDDP肿瘤耐药的作用。方法采用透射电子显微镜、原子力显微镜及粒度分析对制备的CDDP/NGO@MH纳米递药系统进行表征,邻苯二胺法测定CDDP的载药量,无膜溶出法研究其体外释放,紫外吸收光谱检测其GSH耗竭能力,亚甲基蓝溶液验证其类芬顿活性,噻唑蓝(MTT)法考察其对人乳腺癌细胞MDA-MB-231的体外抑制活性。结果制备的CDDP/NGO@MH纳米药物形态为片状,电位为-20 mV,粒径约400 nm,表面分散着大量50nm左右的MnO2纳米粒;MnO2含量为5.4%,CDDP的载药量高达23%,在pH 5.5的酸性环境中释放迅速,具有良好的催化类芬顿活性及GSH耗竭能力;体外细胞实验证实CDDP/NGO@MH中的CDDP和MnO2对人乳腺癌细胞MDA-MB-231具有协同杀伤作用。结论成功构建纳米递药系统CDDP/NGO@MH,实现了对CDDP的高效装载,具有化疗增敏和逆转GSH介导的CDDP肿瘤耐药的作用。
Objective To prepare a high cisplatin(CDDP)-loaded and manganese dioxide-modified nano-grapheme oxide(NGO) drug delivery system CDDP/NGO@MH, and to study its effects on the reverse of glutathione(GSH)-mediated CDDP resistance. Methods The prepared CDDP/NGO@MH nano-drug delivery system was characterized by transmission electron microscope, atomic force microscope and particle size analysis. CDDP was determined by o-phenylenediamine method. Its release in vitro was studied by membrane-free dissolution method, and its Fenton-like activity was verified by methylene blue solution. The ability of GSH depletion was verified by ultraviolet absorption spectra. And its in vitro inhibitory activity against MDA-MB-231 cells was evaluated by methyl thiazolyl tetrazolium(MTT) assay. Results The prepared CDDP/NGO@MH nanoparticles was in sheet shape, with a potential of-20 mV, particle size of about 400 nm, and a large number of MnO2 nanoparticles with particle size of around 50 nm dispersed on the surface. The MnO2 content was 5.4%, the drug load of CDDP was up to 23%, and it released fast in the acidic environment of pH 5.5, showing good catalytic Fenton-like activity and GSH depletion ability. Cell experiments in vitro proved that cisplatin and manganese dioxide in CDDP/NGO@MH had synergistic killing effect on MDA-MB-231 cell line. Conclusion The nanomaterial drug delivery system CDDP/NGO@MH was successfully constructed. It could achieve a high drug loading rate for CDDP, effectively realize the chemotherapeutic sensitization and reverse the GSH-mediated cisplatin resistance of tumor.
作者
罗千歌
石欣怡
丁劲松
周文虎
LUO Qiange;SHI Xinyi;DING Jinsong;ZHOU Wenhu(Xiangya School of Pharmaceutical Sciences,Central South University,Changsha,Hunan,410013,China)
出处
《肿瘤药学》
CAS
2021年第2期158-164,共7页
Anti-Tumor Pharmacy
基金
国家自然科学基金(21804144,U1903125)
中南大学创新驱动工程基金(20170030010004)。
关键词
顺铂
氧化石墨烯
二氧化锰
肿瘤耐药
透明质酸
Cisplatin
Graphene oxide
Manganese dioxide
Tumor resistance
Hyaluronic Acid
作者简介
罗千歌,女,硕士研究生,研究方向:纳米粒药物递送;通信作者:周文虎,男,博士,教授,研究方向:纳米粒药物递送和纳米材料表界面应用研究。
