title: Folate-conjugated beta-cyclodextrin-based polymeric micelles with enhanced doxorubicin antitumor efficacy.
abstract: In order to enhance the antitumor effects of doxorubicin (DOX), a novel micellar vector with high DOX loading and tumor targeting function based on folate-conjugated amphiphilic copolymer folate-poly(ethylene glycol)-poly(d,l-lactide)-β-cyclodextrin (FA-PEL-CD) was constructed. Cytotoxicity and cellular uptake experiments were performed in HeLa, KB, and A549 cell lines expressing different amounts of folate receptors in order to evaluate the targeting effect of the folate modification. The antitumor experiments performed in a KB cell-xenografted nude mouse model showed that the treatment with 10mg/kg DOX loaded FA-PEL-CD micelles achieved approximately 86% of tumor growth inhibition compared to the control. Ex vivo fluorescence imaging experiments and histological examination confirmed that folate modification can enhance the antitumorigenesis efficacy and reduce the cardiotoxicity of DOX. These results suggest that FA-PEL-CD copolymer-based micelles are promising nanocarriers for targeted doxorubicin delivery, with improved antitumor efficacy and reduced toxicity in normal tissues.
authors: College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou 310058, China.
authors: Lu
authors: L
authors: Zhang
authors: College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou 310058, China.
authors: Jiafei
authors: J
authors: Lu
authors: College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou 310058, China.
authors: Yangmin
authors: Y
authors: Jin
authors: Ministry of Education (MOE) Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, 38 Zheda Road, Hangzhou 310027, China; College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou 310058, China. Electronic address: lyqiu@zju.edu.cn.
authors: Liyan
authors: L
authors: Qiu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011108:Polymers / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D008823:Micelles; D011108:Polymers; D047392:beta-Cyclodextrins; D004317:Doxorubicin; D005492:Folic Acid; C031215:betadex
keywords: Anti-tumor; Doxorubicin; Folate; Polymeric micelles; β-Cyclodextrin