title: Targeted delivery of anticancer drugs by aptamer AS1411 mediated Pluronic F127/cyclodextrin-linked polymer composite micelles.
abstract: Aptamers are single-stranded RNA or DNA ligands that can specifically bind to various molecular targets with high affinity. Owing to this unique character, they have become increasingly attractive in the field of drug delivery. In this study, we developed a multifunctional composite micelle (CM) with surface modification of aptamer AS1411 (Ap) for targeted delivery of doxorubicin (DOX) to human breast tumors. This binary mixed system consisting of AS1411 modified Pluronic F127 and beta-cyclodextrin-linked poly(ethylene glycol)-b-polylactide could enhance DOX-loading capacity and increase micelle stability. Cellular uptake of CM-Ap was found to be higher than that of untargeted CM due to the nucleolin-mediated endocytosis effect. In vivo study in MCF-7 tumor-bearing mice demonstrated that the AS1411-functionalized composite micelles showed prolonged circulation time in blood, enhanced accumulation in tumor, improved antitumor activity, and decreased cardiotoxicity. In conclusion, aptamer-conjugated multifunctional composite micelles could be a potential delivery vehicle for cancer therapy.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China. Electronic address: lyqiu@zju.edu.cn.
authors.forename: Liyan
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D052157:Aptamers, Nucleotide; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003505:Cyclodextrins / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D051379:Mice; D008823:Micelles; D050997:Nanomedicine / Q000379:methods; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: C513936:AGRO 100; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D003505:Cyclodextrins; D008823:Micelles; D009838:Oligodeoxyribonucleotides; D047392:beta-Cyclodextrins; D020442:Poloxamer; D011092:Polyethylene Glycols; D004317:Doxorubicin; C031215:betadex
keywords: Aptamer; Composite micelles; Cyclodextrin; Doxorubicin; Pluronic F127