Self-assembly of pH-sensitive micelles for enhanced delivery of doxorubicin to melanoma cells

Polymeric micelles have attracted much attention in the field of anticancer drug delivery system because of their special properties. However, the slow drug release rate of micelles after reaching tumor cells is still considered to be a major problem. Therefore, we constructed a new orthoester-based pH-sensitive polyethylene glycol–hydroxydodecanoic acid (PAE) polymer to form doxorubicin-loaded micelles (DOX/PAE). DOX/PAE micelles with uniform particle size showed pH-sensitive drug release behavior in vitro. And the in vitro cytotoxicity studies showed that blank PAE micelles were nontoxic to cells while DOX/PAE micelles could inhibit the growth of tumor cells in a concentration-dependent manner. Furthermore, cellular uptake studies showed that DOX/PAE micelles were uptaken by tumor cells and transported into the nucleus to achieve the effect of killing tumor cells. The results of the uptake mechanism showed that clathrin and macrophage mediated endocytic pathways played important roles in internalization of DOX/PAE micelles. Altogether, the above results show that pH-sensitive PAE micelles have potential in anticancer drug delivery.