title: Design and Validation of PEG-Derivatized Vitamin E Copolymer for Drug Delivery into Breast Cancer.
abstract: This study examined the ability of amphiphilic poly(ethylene glycol) (PEG) derivatives to assemble into micelles for drug delivery. Linear PEG chains were modified on one end with hydrophobic vitamin E succinate (VES), and PEG and VES were mixed in different molar ratios to make amphiphiles, which were characterized in terms of critical micelle concentration (CMC), drug loading capacity (DLC), serum stability, tumor spheroid penetration and tumor targeting in vitro and in vivo. The amphiphile PEG5K-VES6 (PAMV6), which has a wheat-like structure, showed a CMC of 3.03 × 10(-6) M, good serum stability, and tumor accumulation. The model drug, pirarubicin (THP), could be efficiently loaded into PAMV6 micelles at a DLC of 24.81%. PAMV6/THP micelles were more effective than THP solution at inducing cell apoptosis and G2/M arrest in 4T1 cells. THP-loaded PAMV6 micelles also inhibited tumor growth much more than free THP in a syngeneic mouse model of breast cancer. PAMV6-based micellar systems show promise as nanocarriers for improved anticancer chemotherapy.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.forename: Qinhui
authors.initials: Q
authors.lastname: Liu
authors.forename: Wenyao
authors.initials: W
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Chengdu, China , 610041.
authors.forename: Hanmei
authors.initials: H
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Shiyun
authors.initials: S
authors.lastname: Pu
authors.forename: Jiangying
authors.initials: J
authors.lastname: Kuang
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Su
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University , Chengdu, China , 610041.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jinhan
authors.initials: J
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D018874:Spheroids, Cellular / Q000378:metabolism; D014810:Vitamin E / Q000737:chemistry* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D014810:Vitamin E; D011092:Polyethylene Glycols; D004317:Doxorubicin; C027260:pirarubicin