Monodispersed calcium carbonate nanoparticles modulate local pH and inhibit tumor growth in vivo

Abstract

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. Biochemical simulations indicate that the dissolution of calcium carbonate nanoparticles (nano-CaCO3) dissolution in vivo increases pH asymptotically to 7.4. We developed two independent facile methods to synthesize monodisperse non-doped vaterite nano-CaCO3 with distinct size range between 20 and 300 nm. Using murine models of cancer, we demonstrate that the selective accumulation of nano-CaCO3 in tumors increases tumor pH over time. The associated induction of tumor growth stasis is putatively interpreted as a pHe increase. This study establishes an approach to prepare nano-CaCO3 over a wide particle size range, a formulation that stabilizes the nanomaterials in aqueous solutions, and a pH-sensitive nano-platform capable of modulating the acidic environment of cancer for potential therapeutic benefits.

Nano-antacids enhance pH neutralization beyond their bulk counterparts: synthesis and characterization

“…23 Colloidally stable particles may have further utility as pH neutralizers in other biological conditions. 1,15,24 To determine vaterite’s feasibility for pH neutralization in vivo , we studied the size and stability of these particles in different solvents, using time-resolved dynamic light scattering (TR-DLS) for 30 minutes.…”

Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy Using a CaCO3 Mineralized Metal–Organic Framework

“…[8] In particular,asone of the major inorganic substances produced in natural organisms,C aCO 3 has been applied as at ypical biomaterial to build smart carriers to deliver genes,enzymes, and drugs. [10] However,i ti sr arely reported that nanocarriers were intentionally designed to be encapsulated by CaCO 3 to realize leakage-free and controlled-release drug delivery for cancer therapy.Notably,the utilization of CaCO 3 has an irreplaceable role in improving the anticancer activity of DHA. [10] However,i ti sr arely reported that nanocarriers were intentionally designed to be encapsulated by CaCO 3 to realize leakage-free and controlled-release drug delivery for cancer therapy.Notably,the utilization of CaCO 3 has an irreplaceable role in improving the anticancer activity of DHA.…”

Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment

“…Achilefu group synthesized CaCO 3 NPs to modulate the tumour environment. 200 CaCO 3 can decompose gradually under mild acidic environment (pH ~6.8) into Ca 2+ and CO 2 , and the pH can be modulated by consuming protons at the same time. The animal experiment further confirmed the tumour inhibition effect of these NPs.…”