In situ generation of biocompatible amorphous calcium carbonate onto cell membrane to block membrane transport protein - A new strategy for cancer therapy via mimicking abnormal mineralization

Herein, our aim is to develop a drug-free method without obvious side effects to treat cancer through biomineralization of biocompatible inorganic nanomaterials targeting onto cells' membrane to block transport proteins. We selected chondroitin sulfate as optimal target agent and linker to induce the in situ biomineralization of exogenous Ca2+ and CO32- at safe concentration to generate biocompatible calcium carbonate (CaCO3) nanostructures targeting onto cancer cells' membrane. The in vitro and in vivo assays indicated that the generated CaCO3 nanostructures could significantly inhibit the proliferation of cancer cells. Mechanism studies demonstrated that the mineralized CaCO3 nanostructures could bind with 66 membrane proteins. Deeply research revealed that the CaCO3 nanostructures could mainly block transport proteins, e.g. sodium/potassium-transporting ATPase, leading to the collapse of the mitochondria) membrane potential and the increase of the lactate dehydrogenase release into medium, and finally modulated cell cycle and induced the apoptosis of cancer cells. Our results may introduce promising possibilities for efficient and specific cancer treatment by producing biocompatible nanomaterials to block transport proteins. (C) 2019 Elsevier Inc. All rights reserved.