One of the long-range goals of our laboratory is to determine specific conditions to control intercalation and release of drug layered nanocarriers based on inorganic nanoparticles of zirconium phosphate (ZrP). To contribute to this long-range goal, our studies have focused on the individual and combined intercalation of doxorubicin (DOX) and cisplatin (CisPt) anticancer drugs in ZrP and the surface modification of the intercalated materials with Zr(IV) and m-PEG-PO3. 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 will improve biocompatibility and will provide a modifiable terminal for specific nanoparticle-receptor recognition. Recent results show that the individual intercalation of CisPt and DOX was successful, obtaining an interlayer distance of 9.7 and 21 Å, respectively. Cointercalated products of CisPt and DOX showed two overlapped diffraction peaks at 9.7 and 10.6 Å, consistent with CisPt and DOX intercalation, respectively. Surface modification of DOX-intercalated ZrP nanoparticles (DOX@ZrP) was also performed. 31PMAS NMR data shows a new peak at -26 ppm corresponding to the PO43-groups from m-PEG-PO3coordinated with Zr(IV) on the surface. A preliminary MTS cell viability assay reveals that m-PEG-PO3/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-PEG-PO3/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 materials for cancer treatment could prove to represent a new strategy for nanotherapeutics.

Surface modification of layered structured nanomaterials for drug delivery

2019 Spring National Meeting

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