Our work focus is on the use of layered zirconium phosphate (ZrP) nanoparticles for anticancer drug delivery. We have prepared doxorubicin (DOX)-intercalated ZrP nanoparticles, with an interlayer distance of 21 Å, as well as cisplatin (CisPt)-intercalated ZrP nanoparticles (with an interlayer distance of 9.7 Å) that proved to be active in cell viability studies. We have recently combined intercalation of DOX and CisPt in ZrP as well performed surface modification of the intercalated materials with Zr(IV) and methy-polyethyleneglycol phosphate (m-PEG-PO). Combination of DOX and CisPt should induce a synergistic effect reducing drug resistance when intercalated in ZrP while contributing to selectivity due to the enhanced permeability and retention (EPR) effect of nanoparticles in tumor tissue. Surface PEGylation of intercalated nanoparticles improves biocompatibility and provide a modifiable terminal for specific nanoparticle-receptor recognition. Cointercalated products of CisPt and DOX showed two overlapped diffraction peaks at 9.7 and 20.6 Å, consistent with CisPt and DOX intercalation, respectively. For surface modified DOX-intercalated ZrP nanoparticles (DOX@ZrP), PMAS NMR data shows a new peak at -27 ppm corresponding to the PO groups from m-PEG-PO coordinated with Zr(IV) on the surface. MTS cell viability assays reveal that m-PEG-PO /Zr(IV)/DOX@ZrP exhibits ~20% higher cytotoxicity than free DOX and the other ZrP materials when human prostate cancer PC3 cells are exposed for 48 h. In addition, MTS assay performed for m-PEGPO /Zr(IV)/CisPt@ZrP show significant viability reduction at 1.5 and 2 μM while no significant change occurred for the non-PEGylated samples. Results of in-vitro drug release as well as cytotoxicity studies with breast cancer cell lines for both anticancer agents iindicate that the use of these layered nanomaterials of platelet morphology for cancer treatment are promising as new nanocarriers.

Anticancer drug delivery using layered zirconium phosphate nanoparticles

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