title: Isomeric folate-conjugated polymeric micelles bind to folate receptors and display anticancer effects.
abstract: The present study aimed to prepare and evaluate polymeric micelles conjugated with folic acid through α- or γ-carboxyl groups for antitumor efficacy. The isomeric block copolymers, α- and γ-folate-polyethyleneglycol- distearoyl phosphatidylethanolamine (α- and γ-Fol-PEG-DSPE), were produced by solid phase peptide synthesis. Three types of doxorubicin (DOX)-loaded polymeric micelles (MPEG-DSPE-DOX and α- / γ-Fol-PEG-DSPE- DOX micelles) were prepared via the film formation method. Compared with MPEG-DSPE-DOX micelles, the α- / γ-Fol-PEG-DSPE-DOX micelles presented a higher cellular uptake behavior in the live cell study. Cell viability percentages were 81.8%, 57.3%, 56.6% at 2 hours for MPEG-DSPE-DOX, α- and γ-Fol-PEG-DSPE- DOX micelles, respectively (p<0.05). Using the KB xenograft tumor model, both α- and γ-folate-conjugated micelles were found to have better antitumor effects with lower toxicity in comparison with MPEG-DSPE-DOX micelles. No difference in in vivo antitumor efficacy was found between α-and γ-Fol-PEG-DSPE-DOX micelles. The folate-conjugated micelles might be a potentially useful strategy for tumor targeting of therapeutic agents, whether grafting with folic acid through α- or γ-carboxyl groups.
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China E-mail : liumin@shmu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Dong
authors.forename: Zuo-Xu
authors.initials: ZX
authors.lastname: Xie
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.forename: Wei-Yue
authors.initials: WY
authors.lastname: Lu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D005492:Folic Acid / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007624:KB Cells; D051379:Mice; D008823:Micelles; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011108:Polymers; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D058973:Folate Receptors, GPI-Anchored; D008823:Micelles; D010714:Phosphatidylethanolamines; D011108:Polymers; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005492:Folic Acid