title: Enhanced uptake and cytotoxity of folate-conjugated mitoxantrone-loaded micelles via receptor up-regulation by dexamethasone.
abstract: Folate conjugated amphiphilic polymeric micelles have attracted much attention for active targeted delivery of drugs in folate receptor α (FR-α) positive tumors. However, the efficacy improvement of targeted delivery folate-based nanovehicles was limited by the abundance of FR-α on the surface of tumor cells. Recently, it was found that FR-α expression of Hela cells could be up-regulated by modulators such as dexamethasone, which open a new avenue to enhance the efficiency of targeted delivery from the biological view. In this study, folate-conjugated or plain lipid-core micelles loaded with fluorescent coumarin 6 or mitoxantrone (MTN) were prepared by self-assembly. In addition, FOLR1 mRNA and cell surface FR-α levels were evaluated in Hela cells with dexamethasone treatment. The endocytosis of folate-conjugated or plain micelles loaded with coumarin 6 was examined with confocal microscopy and flow cytometry, which displayed that folate-conjugated micelles can be internalized more efficiently in dexamethasone-treated Hela cells than in normal Hela cells. Moreover, the antitumor activity of folate-conjugated micellar MTN was also improved through up-regulation of FR-α. Therefore, FR-α up-regulation using modulators has great potential to improve the therapeutic efficacy of folate-conjugated nanovehicles in some FR-α positive tumors via receptor-mediated endocytosis.
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, The Key Laboratory of Biomedical Material of Tianjin, Tianjin 300192, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Man
authors.initials: M
authors.lastname: Guan
authors.forename: Jingjie
authors.initials: J
authors.lastname: Wang
authors.forename: Lingrong
authors.initials: L
authors.lastname: Liu
authors.forename: Qiqing
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry; D003907:Dexamethasone / Q000008:administration & dosage*; D004705:Endocytosis / Q000187:drug effects; D058975:Folate Receptor 1 / Q000096:biosynthesis / Q000235:genetics; D005492:Folic Acid / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D058975:Folate Receptor 1; D008823:Micelles; D010714:Phosphatidylethanolamines; D012333:RNA, Messenger; D013844:Thiazoles; C517282:coumarin 6; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D003907:Dexamethasone; D005492:Folic Acid; D008942:Mitoxantrone