title: Synergistic Therapy of Doxorubicin and miR-129-5p with Self-Cross-Linked Bioreducible Polypeptide Nanoparticles Reverses Multidrug Resistance in Cancer Cells.
abstract: Although microRNAs (miRs) are short endogenous noncoding RNAs playing a central role in cancer initiation 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 bioreducible environment. 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/ADR cells. Furthermore, miR-129-5p also partially diminished cyclin-dependent kinase 6 (CDK6), and synergized with DOX to simultaneously decrease S phase and induce G2 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.
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Key Lab for Health Informatics of Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, People's Republic of China.
authors.forename: Huqiang
authors.initials: H
authors.lastname: Yi
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Key Lab for Health Informatics of Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, People's Republic of China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Key Lab for Health Informatics of Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sheng
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Key Lab for Health Informatics of Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Key Lab for Health Informatics of Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Key Lab for Health Informatics of Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, People's Republic of China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Key Lab for Health Informatics of Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, People's Republic of China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects; D003131:Combined Modality Therapy; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D055503:Protein Multimerization; D014407:Tumor Cells, Cultured
chemical_list: D003432:Cross-Linking Reagents; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D010455:Peptides; D004317:Doxorubicin