title: Long circulating self-assembled nanoparticles from cholesterol-containing brush-like block copolymers for improved drug delivery to tumors.
abstract: Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.
authors.affiliation: Department of Pharmaceutical Sciences, ‡Polymer Program, Institute of Materials Science, §Department of Chemistry, ∥Department of Allied Health Sciences, University of Connecticut , Storrs, Connecticut 06269, United States.
authors.forename: Thanh-Huyen
authors.initials: TH
authors.lastname: Tran
authors.forename: Chi Thanh
authors.initials: CT
authors.lastname: Nguyen
authors.forename: Laura
authors.initials: L
authors.lastname: Gonzalez-Fajardo
authors.forename: Derek
authors.initials: D
authors.lastname: Hargrove
authors.forename: Donghui
authors.initials: D
authors.lastname: Song
authors.forename: Prashant
authors.initials: P
authors.lastname: Deshmukh
authors.forename: Lalit
authors.initials: L
authors.lastname: Mahajan
authors.forename: Dennis
authors.initials: D
authors.lastname: Ndaya
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
authors.forename: Rajeswari M
authors.initials: RM
authors.lastname: Kasi
authors.forename: Xiuling
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D002784:Cholesterol