Synthesis of Thermo-Sensitive Micellar Aggregates Self-Assembled from Biotinylated PNAS-b-PNIPAAm-b-PCL Triblock Copolymers for Tumor Targeting

The stimuli-sensitive diblock copolymer poly(N-acroyloxysuccinimide)-b-poly(N-isopropylacrylamide) (PNAS-b-PNEPAAm) was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. By using the terminal carboxyl group of the diblock copolymer to initiate the ring-opening polymerization of epsilon-caprolactone (CL), the amphiphilic PNAS-b-PNIPAAm-b-PCL triblock copolymer was further synthesized. The triblock copolymer was characterized by NMR, IR, and SEC-MALLS. To enhance the internalization to tumor cells, biotin was introduced into the triblock copolymer. The LCST of biotinylated PNAS-b-PNIPAAm-b-PCL was about 35.3 degrees C. The formation of micellar aggregates (MAs) self-assembled from biotinylated PNAS-b-PNIPAAm-b-PCL was confirmed by CMC and TEM. The cell viability study demonstrated that the MAs have a low cytotoxicity. The antitumor drug doxorubicin (Dox) was loaded in the MAs, and in vitro release behavior of Dox showed the MAs exhibited thermo-sensitive drug release. The confocal microscopy studies confirmed that, with pretreatment of biotin-transferrin, the self-assembled MAs could specifically bind to tumor cells, indicating that the multi functional MAs Could be used as a promising drug carrier for tumor targeting.