Redox-responsive comparison of diselenide micelles with disulfide micelles

Redox-responsive block copolymer micelles have been studied extensively as drug carriers. In this study, tri-block copolymers, methoxyl poly(ethylene glycol)-b-poly(ε-caprolactone)-SeSe-b-poly(ε-caprolactone)-b-methoxyl-poly(ethylene glycol) (mPEG-PCL-SeSe-PCL-mPEG) and methoxyl poly(ethyleneglyco)-b-poly(ε-caprolactone)-SS-b- poly(ε-caprolactone)-b-methoxyl-poly(ethylene glycol) (mPEG-PCL-SS-PCL-mPEG), were synthesized to investigate the redox sensitivity differences between diselenide and disulfide micelles. The changes of micelles in size and structure were investigated under conditions with glutathione (GSH) or H 2 O 2 . The results showed that the size and PDI of (mPEG-PCL-Se) 2 micelles presented more significant variations under redox condition in comparison with (mPEG-PCL-S) 2 micelles. The DOX released faster and more from diselenide micelles than disulfide micelles. The half maximal inhibitory concentration (IC 50 ) of (mPEG-PCL-Se) 2 /DOX micelles was lower than that of (mPEG-PCL-S) 2 /DOX micelles against 4T1 and Hela cells. The amount of intracellular drug release from diselenide micelles was higher than from disulfide micelles in Hela cells with GSH 4.6 mM. Therefore, the (mPEG-PCL-Se) 2 micelles similar to (mPEG-PCL-S) 2 micelles are stimuli-responsive and may be more sensitive drug carriers. The polymer micelles containing diselenide or disulfide with similar molecular structure are prepared to investigate the redox sensitivity differences. Both micelles have redox sensitivity and capability to enter into 4T1 cells and Hela cells. (mPEG-PCL-Se) 2 micelles present more significant sensitivity and lower IC 50 against cancer cells than disulfide micelles. The diselenide micelles may be more sensitive platforms and be suit to tumor cells in which GSH is less than 10 mM.