Folate-conjugated pH-responsive nanocarrier designed for active tumor targeting and controlled release of doxorubicin

A novel type of amphiphilic pH-responsive folate-poly（ε-caprolactone）- block-poly（ 2-hydroxyethylmethacrylate ）-co-poly（ 2-（ dimethylamino ）-ethylmethacrylate ） （FA-PCL-b-P（HEMA-co-DMAEMA）） （MFP） block copolymers were designed and synthe- sized via atom transfer radical polymerization （ATRP） and ring opening polymerization （ROP） techniques. The molecular structures of the copolymers were confirmed with IH NMR, FTIR and GPC measurements. The critical micelle concentration （CMC） of MFP in aqueous solution was extremely low （about 6.54 mglL）. The in vitro release behavior of DOX-Ioaded micelles was significantly accelerated when the pH value of solution decreased from 7.4 to 5.0. In vitro antitumor efficiency was evaluated by incubating DOX- loaded micelles with Hela cells. The results demonstrated that this copolymer possessed excellent biocompatibility, and FA-decorated micelles MFP showed higher cellular uptake than those micelles without the FA moiety, indicating their unique targetability. These folate-conjugated biodegradable micelles are highly promising for targeted cancer chemothe-rapy.