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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&lt;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.

Isomeric Folate-Conjugated Polymeric Micelles Bind to Folate Receptors and Display Anticancer Effects