title: Preparation of tri-block copolymer micelles loading novel organoselenium anticancer drug BBSKE and study of tissue distribution of copolymer micelles by imaging in vivo method.
abstract: BBSKE (1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)] ethane, PCT: CN02/00412) is a novel organoselenium anticancer drug that plays a role in anticancer through inhibiting TrxR (thioredoxin reductase). In this study, we prepared a tri-block copolymer micelles loading BBSKE utilizing the amphiphilic tri-block copolymers (PEG6000-PLA6000) which we synthesized. And then the characters of the copolymer micelles were investigated. When packaged in polymeric micelles, the water solubility of BBSKE was improved to 0.21 mg/ml. The IC(50) were 7.14 microM, 5.05 microM and 4.23 microM when MCF-7 breast cancer cells were treated with BBSKE after 24h, 48h and 72h. The inhibition effect of polymeric micelles to MCF-7 tumor cells was bettered when folate, whose receptor was highly expressed in various tumors, was coated on the surface of these nanoparticles. Finally, by adopting a new way of imaging in vivo, we studied the distribution of micelles in nude mice with and without MCF-7 tumor. The results demonstrated that this copolymer micelles loading BBSKE can accumulate into tumor efficiently.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Liu
authors.forename: Jianing
authors.initials: J
authors.lastname: Fu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tan
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Ren
authors.forename: Zuofu
authors.initials: Z
authors.lastname: Peng
authors.forename: Huihui
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D007773:Lactates / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D016566:Organoselenium Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D014018:Tissue Distribution
chemical_list: C478160:(1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone))ethane; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007773:Lactates; D008823:Micelles; D016566:Organoselenium Compounds; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols