title: Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer.
abstract: Co-delivery of microRNAs and chemotherapeutic drugs into tumor cells is an attractive strategy for synergetic breast cancer therapy due to their complementary mechanisms. In this work, a core-shell nanocarrier coated by cationic albumin was developed to simultaneously deliver miRNA-34a and docetaxel (DTX) into breast cancer cells for improved therapeutic effect. The co-delivery nanocarriers showed a spherical morphology with an average particle size of 183.9 nm, and they efficiently protected miRNA-34a from degradation by RNase and serum. Importantly, the nanocarriers entered the cytosol via a caveolae-mediated pathway without entrapment in endosomes/lysosomes, thus improving the utilization of the cargo. In vitro, the co-delivery nanocarriers suppressed the expression of anti-apoptosis gene Bcl-2 at both transcription and protein levels, inhibited tumor cell migration and efficiently induced cell apoptosis and cytotoxicity. In vivo, the co-delivery nanocarriers prolonged the blood circulation of DTX, enhanced tumor accumulation of the cargo and significantly inhibited tumor growth and metastasis in 4T1-tumor bearing mice models. Taken together, the present nanocarrier co-loading with DTX and miRNA-34a is a new nanoplatform for the combination of insoluble drugs and gene/protein drugs and provides a promising strategy for the treatment of metastatic breast cancer.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Xin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P.R. China.|Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, P.R. China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D021941:Caveolae / Q000737:chemistry*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000097:blood; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009362:Neoplasm Metastasis; D034622:RNA Interference; D020871:RNA Stability; D051381:Rats; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel