Synergistic Therapy of Doxorubicin and miR-129-5p with Self-Cross-Linked Bioreducible Polypeptide Nanoparticles Reverses Multidrug Resistance in Cancer Cells
Yi, Huqiang; Liu, Lanlan; Sheng, Nan; Li, Ping; Pan, Hong; Cai, Lintao; Ma, Yifan
刊名BIOMACROMOLECULES
2016
英文摘要Although microRNAs (miRs) are short endogenous noncoding RNAs playing a central role in cancerinitiation and progression, their therapeutic potential in overcoming multidrug resistance (MDR) remains unclear. In the present study, we developed self-cross-linked biodegradable poly(ethylene glycol)-b-poly(L-lysine)-b-poly(L-cysteine) (LCss) polypeptide nanoparticles to codeliver DOX and miR-129-5p, which aimed to overcome MDR in cancer cells. The results showed that LCss nanoparticles effectively coencapsulated DOX and miR with great stability, but quickly disassembled and released their payload in a bioreducibleenvironment. The codelivery of miR-129-5p and DOX with LCss (DLCss/miR) significantly increased miR-129-5p expression over 100-fold in MCF-7/ADR cells, which effectively overcame MDR by directly inhibiting P-glycoprotein (P-gp), thereby increasing intracellular DOX accumulation and cytotoxicity in MCF-7/ADRcells. Furthermore, miR-129-5p also partially diminished cyclin-dependent kinase 6 (CDK6), and synergizedwith DOX to simultaneously decrease S phase and induce G(2) phase cell cycle arrest, thereby further enhancing the chemosensitivity of MCF-7/ADR cells. Hence, redox-responsive LCss nanoparticles are potent nanocarrier for combinational drug-miR therapy, which could be a promising strategy to overcome MDR in cancer cells.
收录类别SCI
原文出处http://pubs.acs.org/doi/abs/10.1021/acs.biomac.6b00141
语种英语
内容类型期刊论文
源URL[http://ir.siat.ac.cn:8080/handle/172644/10678]  
专题深圳先进技术研究院_医药所
作者单位BIOMACROMOLECULES
推荐引用方式
GB/T 7714
Yi, Huqiang,Liu, Lanlan,Sheng, Nan,et al. Synergistic Therapy of Doxorubicin and miR-129-5p with Self-Cross-Linked Bioreducible Polypeptide Nanoparticles Reverses Multidrug Resistance in Cancer Cells[J]. BIOMACROMOLECULES,2016.
APA Yi, Huqiang.,Liu, Lanlan.,Sheng, Nan.,Li, Ping.,Pan, Hong.,...&Ma, Yifan.(2016).Synergistic Therapy of Doxorubicin and miR-129-5p with Self-Cross-Linked Bioreducible Polypeptide Nanoparticles Reverses Multidrug Resistance in Cancer Cells.BIOMACROMOLECULES.
MLA Yi, Huqiang,et al."Synergistic Therapy of Doxorubicin and miR-129-5p with Self-Cross-Linked Bioreducible Polypeptide Nanoparticles Reverses Multidrug Resistance in Cancer Cells".BIOMACROMOLECULES (2016).
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