Layered Zirconium Phosphate Nanocarriers for Mitoxantrone: Advancing Targeted Chemotherapy

Layered zirconium phosphate nanoparticles (ZrPs), inorganic structures with a layered composition of zirconium atoms linked by phosphate groups, exhibit no cytotoxic effects on healthy or cancer cells, indicating a strong safety profile. We are investigating ZrP as a carrier for mitoxantrone (MTX), an anticancer drug that inhibits topoisomerase II and disrupts DNA synthesis but lacks selectivity between healthy and cancer cells. MTX shows prolonged retention in the body, with potential systemic toxicity affecting thyroid, hepatic, and cardiac tissues. We report a strategy to reduce systemic toxicity and protect healthy tissues from MTX by intercalating MTX into ZrP (MTX@ZrP), determining the conditions that affect MTX's release, and evaluating the cytotoxicity of MTX@ZrP on PC3 prostate cancer cells. MTX was intercalated within ZrP, forming MTX@ZrP nanoparticles, which were then characterized by Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, z-potential analysis, and X-ray powder diffraction (XRPD) at different MTX:ZrP molar ratios. XRPD showed that MTX@ZrP has an expanded interlayer distance of 20.0 Å compared to the 7.6 Å interlayer distance of α-ZrP. Thermogravimetric analysis performed on all molar ratios of MTX to ZrP showed that the 1:1 MTX@ZrP molar ratio material had the highest drug loading of 13.8%. A drug release study to determine conditions affecting MTX liberation from ZrP at different pH levels using simulated body fluid and artificial lysosomal fluid showed that this process is pH-dependent. Cell viability studies with the androgen receptor-negative prostate cancer cell line PC3 showed that MTX@ZrP produces a cytotoxic effect. These findings help us envision a possible drug delivery approach that may greatly minimize adverse effects and harm to healthy tissues, offering promises for a more bearable cancer treatment.