title: Copolymeric micelles for delivery of EGCG and cyclopamine to pancreatic cancer cells.
abstract: Our objective was to synthesize a copolymer for delivery and protection of (-)-epigallocatechin gallate (EGCG). Methoxy poly(ethylene glycol)-b-poly[5-methyl-5-(3, 4, 5-trimethoxybenzoyol)-1, 3-dioxan-2-one-co-lactide] [mPEG-b-P(TM-co-LA)] copolymer was synthesized and characterized. The use of gallate containing monomer resulted in a copolymer that could show enhanced drug loading, stability, and sustained release of EGCG from mPEG-b-P(TM-co-LA) micelles as determined using LC/MS. The combination of EGCG and cyclopamine (CyA) displayed remarkable effects on growth inhibition of Mia PaCa-2 pancreatic cancer cells and induction of apoptosis. Although the expression level of Gli-1 was markedly downregulated by cyclopamine treatment, treatment with EGCG significantly inhibited the phosphorylation of EGFR in Mia PaCa-2 cells. Gallate containing copolymer can be used for micellar delivery of EGCG and CyA and the combination of these drugs can target 2 signaling pathways, thereby providing an effective way to treat pancreatic cancer.
authors.affiliation: a School of Life Sciences and Technology , Tongji University, Shanghai, People's Republic of China and Petrochemical Research Institute, PetroChina Company Limited , Beijing , People's Republic of China.
authors.forename: Liming
authors.initials: L
authors.lastname: Sun
authors.forename: Chenlu
authors.initials: C
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008823:Micelles; D010190:Pancreatic Neoplasms; D010766:Phosphorylation; D011091:Polyesters / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000494:pharmacology*
chemical_list: D053823:Hedgehog Proteins; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D014704:Veratrum Alkaloids; C000595446:methoxy poly(ethylene glycol)-b-poly(5-methyl-5-(3,4,5-trimethoxybenzoyol)-1,3-dioxan-2-one-co-lactide) copolymer; D011092:Polyethylene Glycols; D002392:Catechin; C045651:epigallocatechin gallate; D066246:ErbB Receptors; C000541:cyclopamine