title: Cellular internalization of doxorubicin loaded star-shaped micelles with hydrophilic zwitterionic sulfobetaine segments.
abstract: Four arm star-shaped poly(ε-caprolactone)-b-poly((N,N-diethylaminoethyl methacrylate)-r-(N-(3-sulfopropyl)-N-methacryloxyethy-N,N-diethylammoniumbetaine)) (4sPCLDEAS) micelles were loaded with anticancer drug doxorubicin to track their endocytosis in Hela cancer cell line. The effects of mean diameters and surface charges of the drug loaded micelles on the cellular uptake were studied in details. The results demonstrated that the internalization of micelles was both time and energy dependent process. Endocytic pathways including clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis were all involved in the internalization; caveolae-mediated endocytosis was the main pathway for the internalization of 4sPCLDEAS micelles. The assays for cell apoptosis and growth inhibition of tumor spheroids identified that these doxorubicin loaded micelles could induce cell apoptosis and inhibit tumor spheroids growth efficiently, which was even equal to free DOX·HCl. This study provided a rational design strategy for fabricating diverse micellar drug delivery systems with high anticancer efficiency.
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Xiaoxiong
authors.initials: X
authors.lastname: Xie
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Aijing
authors.initials: A
authors.lastname: Lu
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China; State Key Lab of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. Electronic address: luoxl@scu.edu.cn.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Luo
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001622:Betaine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D008689:Methacrylates / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008689:Methacrylates; D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D001622:Betaine; D004317:Doxorubicin; C483727:sulfobetaine; C519537:diethylaminoethyl methacrylate
keywords: Cellular uptake; Drug delivery; Polymeric micelles; Sulfobetaine; Tumor spheroid