CaCO₃ nanoparticles pH-sensitively induce blood coagulation as a potential strategy for starving tumor therapy

Abstract

Based on the starving tumor concept, we first raised an idea that the pH-sensitive Ca2+ release of CaCO3 NPs induced blood coagulation of tumor vessels, and explored the in vitro and in vivo blood coagulation behaviors of CaCO3 NPs by acid stimulus.

Calcium carbonate nano- and microparticles: synthesis methods and biological applications

“…Recently, Li et al synthesized DOX-loaded CaCO 3 NPs using emulsion method to study the pH-responsive drug release. The synthesized particles were of ~ 100 nm size with ~ 49% drug loading capacity (Li et al 2020). The results revealed that at pH 5.0, CaCO 3 NPs released Ca +2 ions causing blood coagulation by catalyzing the formation of thrombin from prothrombin.…”

Engineered nanomedicines for tumor vasculature blockade therapy

“…This material expanded rapidly within minutes under IR light irradiation to achieve local vascular embolization. Recently, a delivery system of a pH‐sensitive calcium carbonate nanoparticle equipped with DOX was prepared (H. Li et al, 2020). The nanoparticle could decompose in the acidic tumor microenvironment, inducing in situ thrombosis, while the released DOX could efficiently kill tumor cells.…”

Thrombin-Loaded TA-CaCO3 Microspheres as a Budget, Adaptable, and Highly Efficient Hemostatic

“…Calcium carbonate (CaCO 3 ) microsphere is a kind of biocompatible hemostatic material with high porosity and strong adsorption capacity without a complex preparation process. − In the form of microspheres, it is capable of being used in irregularly shaped wounds. , As a vector, CaCO 3 microspheres can both encapsulate small molecules of drugs and load lysozyme or other proteins. − More importantly, the safety of CaCO 3 has been proved by the US Food and Drug Administration (FDA) because only 0.15 mM CaCO 3 can be dissolved in water at room temperature, which is lower than the concentration of Ca 2+ in human blood (2.15–2.65 mM). Despite all the advantages mentioned above, the use of CaCO 3 microspheres alone will not stop bleeding quickly. , Hence, combined with the characteristics of the CaCO 3 microspheres, the addition of some thrombins to enhance the hemostatic performance is necessary because thrombin can directly act on the last step of the blood coagulation process and act together with coagulation factors to form insoluble fibrin. This process speeds up the blood clotting. − In clinical settings, the thrombin physiological saline solution is mostly used in the treatment of blood vessels and viscera bleeding with difficult ligation and hemostasis.…”

“…Despite all the advantages mentioned above, the use of CaCO 3 microspheres alone will not stop bleeding quickly. 30,31 Hence, combined with the characteristics of the CaCO 3 microspheres, the addition of some thrombins to enhance the hemostatic performance is necessary because thrombin can directly act on the last step of the blood coagulation process and act together with coagulation factors to form insoluble fibrin. This process speeds up the blood clotting.…”