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MUC-1 aptamer conjugated InP/ZnS quantum dots/nanohydrogel fluorescent composite for mitochondria-mediated apoptosis in MCF-7 cells
Biomaterials Advances ( IF 7.9 ) Pub Date : 2020-08-30 , DOI: 10.1016/j.msec.2020.111469
Zahra Ranjbar-Navazi , Marziyeh Fathi , Elaheh Dalir Abdolahinia , Yadollah Omidi , Soodabeh Davaran

The combined use of nanohydrogels (NHGs) and quantum dots (QDs) has resulted in the development of a nanoscaled drug delivery system (DDS) with fluorescence imaging potential. NHG-QDs composite loaded with anti-cancer drugs could be applied as an effective theranostics for simultaneous diagnosis and therapy of cancer cells. Here, we report on the synthesis of NHG-QDs nanosystem (NS) conjugated with an amino-modified MUC-1 aptamer (Ap) and loaded with hydrophobic paclitaxel (PTX). To effectively target and eradicate breast cancer MCF-7 cells, the nanocomposite was further loaded with the inhibitor of lactate dehydrogenase (LDH), sodium oxamate (SO) (Ap-NHG-QDs-PTX-SO) to inhibit the conversion of pyruvate to lactate via LDH and disrupting glycolysis. Results obtained from in vitro analysis (MTT assay, apoptosis/necrosis assessment, evaluation of mitochondria targeting, and gene expression profiling) revealed that Ap-NHG-QDs-PTX-SO NS could significantly target and inhibit MCF-7 cells and also induce mitochondria-mediated apoptosis. Collectively, the Ap-NHG-QDs-PTX-SO NS is proposed to serve as a robust theranostics for simultaneous imaging and therapy of breast cancer and other types of solid tumors.



中文翻译:

MUC-1适体偶联的InP / ZnS量子点/纳米水凝胶荧光复合物用于线粒体介导的MCF-7细胞凋亡

纳米水凝胶(NHGs)和量子点(QDs)的组合使用已导致开发具有荧光成像潜能的纳米级药物递送系统(DDS)。载有抗癌药物的NHG-QDs复合材料可以用作同时诊断和治疗癌细胞的有效治疗方法。在这里,我们报告与氨基修饰的MUC-1适体(Ap)共轭并负载疏水紫杉醇(PTX)的NHG-QDs纳米系统(NS)的合成。为了有效地靶向和根除乳腺癌MCF-7细胞,该纳米复合材料进一步负载了乳酸脱氢酶(LDH),草酸钠(SO)(Ap-NHG-QDs-PTX-SO)抑制剂以抑制丙酮酸转化为乳酸通过LDH和破坏糖酵解。从体外获得的结果分析(MTT分析,凋亡/坏死评估,线粒体靶向评估和基因表达谱分析)显示,Ap-NHG-QDs-PTX-SO NS可以显着靶向并抑制MCF-7细胞,还可以诱导线粒体介导的凋亡。总体而言,Ap-NHG-QDs-PTX-SO NS被建议用作同时对乳腺癌和其他类型实体瘤进行成像和治疗的强大的诊断学。

更新日期:2020-08-30
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