Enhanced uptake and cytotoxity of folate-conjugated mitoxantrone-loaded micelles via receptor up-regulation by dexamethasone.

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.