title: Polymeric micelles encapsulating fisetin improve the therapeutic effect in colon cancer.
abstract: The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) was discovered to possess antitumor activity, revealing its potential value in future chemotherapy. However, its poor water solubility makes it difficult for intravenous administration. In this study, the monomethyl poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) copolymer was applied to prepare nanoassemblies of fisetin by a self-assembly procedure. The prepared fisetin micelles gained a mean particle size of 22 ± 3 nm, polydisperse index of 0.163 ± 0.032, drug loading of 9.88 ± 0.14%, and encapsulation efficiency of 98.53 ± 0.02%. Compared with free fisetin, fisetin micelles demonstrated a sustained and prolonged in vitro release behavior, as well as enhanced cytotoxicity, cellular uptake, and fisetin-induced apoptosis in CT26 cells. As for in vivo studies, fisetin micelles were more competent for suppressing tumor growth and prolonging survival time than free fisetin in the subcutaneous CT26 tumor model. Furthermore, histological analysis, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, immunohistochemical detection of Ki-67, and microvessel density detection were conducted, demonstrating that fisetin micelles gained increased tumor apoptosis induction, proliferation suppression, and antiangiogenesis activities. In conclusion, we have successfully produced a MPEG-PCL-based nanocarrier encapsulating fisetin with enhanced antitumor activity.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041, P. R. China.
authors.forename: Yishan
authors.initials: Y
authors.lastname: Chen
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.forename: Linjiang
authors.initials: L
authors.lastname: Song
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Weijun
authors.initials: W
authors.lastname: Su
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qian
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000628:therapy*; D004337:Drug Carriers; D005419:Flavonoids / Q000737:chemistry*; D044948:Flavonols; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D008833:Microcirculation; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D005419:Flavonoids; D044948:Flavonols; D019394:Ki-67 Antigen; D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; C017875:fisetin
keywords: biodegradable; colon cancer; drug delivery; fisetin; micelle