title: Vitamin E Succinate-Grafted-Chitosan Oligosaccharide/RGD-Conjugated TPGS Mixed Micelles Loaded with Paclitaxel for U87MG Tumor Therapy.
abstract: The poor therapeutic efficacy of hydrophobic chemotherapeutic drugs is an intrinsic limitation to successful chemotherapy. In the present study, a multitask delivery system based on arginine-glycine-aspartic acid peptide (RGD) decorated vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/RGD-conjugated d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS-RGD) mixed micelles (VeC/T-RGD MM) was first prepared for targeted delivery of a hydrophobic anticancer drug, paclitaxel (PTX), to improve the efficacy of U87MG tumor therapy. VES grafted CSO (VES-g-CSO) and TPGS-RGD were synthesized as nanocarriers, and PTX loaded VeC/T-RGD MM (PTX@VeC/T-RGD MM) was prepared via the organic solvent emulsification-evaporation method. The PTX@VeC/T-RGD MM was 150.2 nm in diameter with uniform size distribution, 5.92% drug loading coefficient, and no obvious particle size changes within 7 days. The PTX@VeC/T-RGD MM showed sustained-release properties in vitro and high cytotoxicity, and could be efficiently taken up by human glioma U87MG cells. The tumor inhibitory rate of PTX@VeC/T-RGD MM treatment in U87MG tumor spheroids and U87MG tumor bearing mice was 49.3% and 88.4%, respectively, which indicated a superior therapeutic effect. PTX@VeC/T-RGD MM did not damage normal tissues in safety evaluations. These findings suggested that PTX@VeC/T-RGD MM could be developed for the delivery of hydrophobic drugs to U87MG tumors.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Yanzuo
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Liu
authors.affiliation: Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai 200062, China.
authors.forename: Zeting
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai 200062, China.
authors.forename: Peihao
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology , Shanghai 200237, China.|Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Feng
authors.identifier: 0000-0003-0427-6998
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D048271:Chitosan / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage; D009842:Oligopeptides / Q000494:pharmacology*; D009844:Oligosaccharides / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D010316:Particle Size; D013386:Succinates / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D009842:Oligopeptides; D009844:Oligosaccharides; D013386:Succinates; D014810:Vitamin E; C047981:arginyl-glycyl-aspartic acid; D048271:Chitosan; D024502:alpha-Tocopherol; C014225:tocophersolan; D017239:Paclitaxel
keywords: PTX; TPGS-RGD; U87MG tumor inhibition; VES-grafted-CSO; mixed micelles