Polymeric micelles with dual thermal and reactive oxygen species (ROS)-responsiveness for inflammatory cancer cell delivery

Abstract

BACKGROUND: The object of this study was to develop a thermally and reactive oxygen species-responsive nanocarrier system for cancer therapy. RESULTS: PPS-PNIPAm block copolymer was designed and synthesised using a combination of living anionic ring-opening polymerization and atom transfer radical polymerization. The synthesized polymer formed micellar aggregates in water and demonstrated dual responsiveness towards temperature and oxidants. Using doxorubicin (DOX) as a model drug, encapsulation and in vitro release of the drug molecules in PPS-PNIPAm nanocarriers confirmed the responsive release properties of such system. Cell uptake of the DOX loaded micelles was investigated with human breast cancer cell line (MCF-7). The results showed Dox-loaded micelles were able to be taken by the cells and mainly reside in the cytoplasma. In the stimulated cells with an elevated level of ROS, more released DOX was observed around the nuclei. In the cytotoxicity experiments, the Dox-loaded micelles demonstrated comparable efficacy to free DOX at higher concentrations, especially on ROS stimulated cells. CONCLUSIONS: These results demonstrated that PPS-PNIPAm nanocarriers possess the capability to respond two typical stimuli in inflammatory cells: temperature and oxidants and can be used in anticancer drug delivery.