Heparosan based negatively charged nanocarrier for rapid intracellular drug delivery.

In this study, a heparosan-DOX conjugate (HDC) was designed and prepared by covalently linking heparosan with anticancer drug doxorubicin (DOX) via "Schiff" base. Due to the amphiphilic nature, the HDC could self-assemble into nanoparticles in aqueous solution of pH 7.4. In spite of the surface charge of HDC nanoparticles was negative, HDC could achieve intracellular delivery of DOX efficiently. Cellular uptake study revealed the endocytosis pathway of heparosan based nanocarrier includes clathrin-mediated endocytosis and macropinocytosis, and the process of endocytosis is energy dependent. This meant the HDC would reach endosomes and behave pH-sensitive DOX release profile due to the inherent property of "Schiff" base. The cytotoxicity assay and flow cytometry analysis demonstrated the cellular uptake of HDC was faster than that of free DOX, showing improved efficacy within short co-incubation period. Furthermore, the HDC nanoparticles were stable in culture medium containing 10% FBS, indicating promising application for drug delivery.