Abstract 1848: Layered zirconium phosphate nanoparticles as anticancer drug carrier

Abstract Layered zirconium phosphate nanoparticles (ZrP), 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. This study aims to reduce systemic toxicity and protect healthy tissues from MTX by intercalating MTX into ZrP (MTX-ZrP) via ion exchange, determining the conditions that affect MTX’s release, and evaluating the cytotoxicity of MTX-ZrP on prostate cancer cells. MTX was intercalated with ZrP nanoparticles, forming MTX-ZrP, which was then characterized by Fourier Transformed infrared spectroscopy, scanning electron microscopy/energy dispersive X-ray spectroscopy, and X-ray powder diffraction at different molar ratios. A drug release study to determine conditions affecting MTX liberation from ZrP at different pHs using simulated body fluid and lysosomal fluid showed that ZrP nanoparticles maintain stable and intercalated MTX at biological pH 7.4. However, at pH 4.5, which simulates the extracellular environment of the tumor, MTX is released, implying that this process is pH-regulated. Cell viability studies with androgen receptor-negative prostate cancer cell line PC3 showed that MTX-ZrP produced a cytotoxic effect. These findings represent the initial phase of a possible drug delivery method that may greatly minimize adverse effects and harm to healthy tissues, offering promise for a more bearable cancer treatment. In the future, we expect to further improve the drug carrier system’s efficacy by modifying the surface of MTX-ZrP, which could significantly enhance its selectivity and specificity. Citation Format: Aleannette Lopez-Cubero, Getsemary Cabrera, Armando Santiago, Yairisis Rivera, Maria M. Rivera, Alianys Rosario, Magaly Martinez-Ferrer, Jorge L. Colon. Layered zirconium phosphate nanoparticles as anticancer drug carrier [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1848.