Abstract

There has been growing interests in nanoparticulate delivery of the natural carotenoid , lutein for anti-cancer therapy. However, the low aqueous solubility of lutein and the poor lutein release from nanocarriers limit its bioavailability and therapeutic outcome. To address this problem, we report a pH-responsive polymer micelle for on-demand delivery of lutein. The selected micelle building polymer was methoxy poly(ethylene glycol)- co -poly(aspartic acid)-imidazole that was ionically crosslinked by biocompatible iron (III). Such imidazole-iron coordination bonding is stable in neutral conditions (e.g. pH 7.4), but it could be ruined under acidic microenvironment (e.g. endosome). A control micelle was also produced with non-responsive PEGylated poly( β -benzyl l -aspartate) (mPEG-PBLA) copolymer . The drug-loaded responsive micelles displayed a hydrodynamic size of 168.2  nm with a lutein loading of 3.5% (w/w) and iron loading of 0.2% (w/w). The pH-responsive release was verified by in vitro release test at pH 7.4 and 5.0. The half maximal inhibitory concentration of the responsive micelles in HeLa cells was ca. 58.4 μM that was significantly lower than that of control micelles. All the results suggested that the triggered cargo release aided the cytosol accumulation of lutein without the delay of therapeutic action. The current work highlighted the stimuli-responsive nanomedicine in on-demand carotenoid delivery.