Surface modification of pharmaceutical nanocarriers with ascorbate residues improves their tumor-cell association and killing and the cytotoxic action of encapsulated paclitaxel in vitro.

PURPOSE: To evaluate the potential of ascorbate as a novel ligand in the preparation of pharmaceutical nanocarriers with enhanced tumor-cell specific binding and cytotoxicity.
METHODS: Palmitoyl ascorbate was incorporated into liposomes at varying concentrations. A stable formulation was selected based on size and zeta potential measurements. A co-culture of cancer cells with GFP expressing non-cancer cells was used to determine the specificity of palmitoyl ascorbate liposome binding. Liposomes were fluorescently labeled to facilitate analysis by flow cytometry and fluorescence microscopy. The cytotoxic action of palmitoyl ascorbate liposomes against a variety of cell types was assayed using a standard metabolic assay. The cytotoxic effect of a low dose of paclitaxel incorporated in palmitoyl ascorbate liposomes on various cell lines was also determined.
RESULTS: Palmitoyl ascorbate liposomes associated preferentially with various cancer cells compared to non-cancer cells in a co-culture model. Palmitoyl ascorbate liposomes exhibited anti-cancer toxicity in numerous cancer cell lines. Furthermore, ascorbate liposomes enhanced the effectiveness of encapsulated paclitaxel compared to paclitaxel encapsulated in 'plain' liposomes.
CONCLUSIONS: Surface modification of liposomes with ascorbate residues represents a novel way to target and kill certain types of tumor cells and additionally can potentiate the effect of paclitaxel delivered by the liposomes.