Redox Responsive Drug Nanocarrier

Multidrug resistance is a main problem for chemotherapeutic and molecular targeting treatment, which decreasing the effect of chemotherapeutic and increasing the difficulty of cancer treatment. Most anticancer drugs are poorly water-solute, resulting in poor bioavailability and increased treatment difficulty and drug side effect. Nanomedicine has the potential to improve the solubility of poorly solute drugs and realize drug controlled release and targeted treatment.This study is focus on redox-responsive TPGS nanomicelles loaded with D-a-tocopherol succinate functionalized prodrug.In the first part, a amphiphilic polymers with redox-responsive properties was synthesized by reversible addition-fragmentation chain transfer polymerization. And hydrophilic PEG was linked with hydrophobic D-a-tocopherol succinate by disulfide bond. This nanomicelles is redox-responsive due to disulfide, monodispersed and high drug-loading. In vitro, redox-responsive drug-loading micelles could inhibit P-gp to increase intercellular drug concentration and redox-responsive release drug to decrease drug leakage and drug toxicity in normal cells. Furthermore, these micelles showed good therapeutic effect to resistance cancer model.The second part is based on the first part that has improved PSSVSV could overcome multidrug resistance in breast solid cancer. Here, drug-loading PSSV micelles was tunable with size. And monodispersed different size micelles with high drug loading were made. PSSVPV micelles also could overcoming multidrug resistance in vitro. Cancer stem cells was cultured via 3D tumor sphere model and 40 nm PSSVPV has more potential of killing cancer stem cells than 80 nm PSSVPV.