Ascorbic Palmitate as a Bifunctional Drug and Nanocarrier of Paclitaxel for Synergistic Anti-Tumor Therapy.

The in vivo application of ascorbate is currently limited by the very high blood concentrations that are required to achieve therapeutic levels in tumors, which needs to exploit a novel drug platform to improve the pharmacokinetics of vitamin C (Vc) and its antitumoral effects. In this study, ascorbyl palmitate (AP), an amphiphilic molecule, is the palmitate acid ester derivative of ascorbic acid, which can be formed a "bifunctional" nanoparticle in which the AP acts not only as an antitumor drug but also as a nanocarrier for encapsulating hydrophobic antitumor drugs such as paclitaxel (PTX). We developed a bifunctional nanocarrier based on AP, which loaded with PTX for synergistic cancer chemotherapy. The resulting PTX-AP nanoparticles (PTX-APNPs) were spherical and had an average size of 294.2 nm based on dynamic light scattering. The in vitro anti-B16F10 cells test of PTX-APNPs revealed an obvious synergistic effect of AP and PTX, and the PTX-APNPs strongly induced cell apoptosis and production of reactive oxygen species. In addition, PTX-APNPs formulation also effectively suppressed the tumorigenicity of B16F10 cells in female C57BL/6 mice without causing severe toxicity. These results suggest that AP-based nanoparticles formulated with paclitaxel are useful for synergistic chemotherapy.