Introduction: The acidic extracellular environment of tumors potentiates their aggressiveness and metastasis, but few methods exist to selectively modulate the extracellular pH (pHe) environment of tumors. Transient flushing of biological systems with alkaline fluids or proton pump inhibitors is impractical and nonselective. Here we report a nanoparticles-based strategy to intentionally modulate the pHe in tumors and restricts it growth.

Methods: We developed two independent facile methods to synthesize monodisperse non-doped vaterite nano-CaCO3 with distinct size range between 20 and 300 nm. Biochemical simulations were used to simulate pH changes in vivo using the particle. In vitro and in vivo assays were used to determine pH changes. IV injections of the nanoparticles were implemented in a xenograft model of fibrosarcoma to determine growth changes.

Results: Biochemical simulations indicate that the dissolution of calcium carbonate nanoparticles (nano-CaCO3) dissolution in vivo increases pH asymptotically to 7.4. Using murine models of cancer, we demonstrate that the selective accumulation of nano-CaCO3 in tumors increases tumor pHe over time. The persistent neutralization of tumor pHe from nano-CaCO3 induces tumor growth stasis.

Conclusions: We have been able to create a novel nanoparticle based on widely existing in vivo components (Calcium and CO3) that safely equilibrates acidic pH of tumors up to normal physiological pH. As expected, this modulation restricts growth of implanted tumors in vivo. Future studies will study the effect of these particles on metastasis, and synergy with other therapeutic modalities.

Citation Format: Avik Som, Ramesh Raliya, Walter Akers, Joseph Ippolito, Srikanth Singamaneni, Pratim Biswas, Samuel Achilefu. Nano-CaCO3 as a novel pH-sensitive nanoparticle platform for cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-232.