Redox resetting of cisplatin-resistant ovarian cancer cells by cisplatin-encapsulated nanostructured lipid carriers

被引:6
作者
Mittal, Disha [1 ]
Biswas, Largee [1 ]
Verma, Anita Kamra [1 ]
机构
[1] Univ Delhi, Dept Zool, Kirori Mal Coll, Nanobiotech Lab, Delhi 110007, India
关键词
ATP7B; cisplatin; GSH; nanostructured lipid carriers; ovarian cancer; reactive oxygen species; redox resetting; EFFLUX TRANSPORTERS ATP7A; OXIDATIVE STRESS; MITOCHONDRIAL-DNA; DRUG-RESISTANCE; GLUTATHIONE; CARCINOMA; MECHANISMS; APOPTOSIS; SYSTEM; ROS;
D O I
10.2217/nnm-2020-0400
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: To sensitize cisplatin (Cis)-resistant ovarian cancer cells toward Cis using Cis-loaded nanostructured lipid carriers (CisNLCs). Materials & methods: CisNLCs were synthesized and characterized using dynamic light scattering, Fourier transform IR and x-ray diffraction (XRD). Sensitivity of PA-1 and CaOV3 cells to Cis and its biotoxicity were assessed. Further, expression of the Cis-resistance markers GSTPi and ATP7B, and apoptotic markers Bax, Bcl2 and Cas9 were quantified by real-time PCR. Results: The size of synthesized CisNLCs was approximately 179.3 +/- 2.32 nm and surface charge was -33.9 +/- 1.47 mV. IC50 was 210 mu g/ml in PA-1 and 500 mu g/ml in CaOV3. CisNLCs modulated reactive oxygen species levels in CaOV3 cells. Reduced GSTPi and decreased Cis efflux via ATP7B sequestration caused Cis to accumulate in cytoplasm, thereby augmenting apoptosis in cells. Conclusion: CisNLCs sensitize CaOV3 by redox resetting, indicating their immense therapeutic potential.
引用
收藏
页码:979 / 995
页数:17
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