Carbonate apatite: effect of serum and impact on the cellular proteome

Abstract

Carbonate apatite (CA) is a synthetic derivative of hydroxyapatite, which we have been exploring as a drug delivery nanocarrier in the context of cancer in vitro and in vivo. This nanocarrier showed great potential delivering anti-cancer drugs, plasmids containing tumour suppressor genes and siRNAs against oncogenes in pre-clinical models. We compared here two formulations of CA—the low-Ca2+ CA (made with 4 mM Ca2+) used for in vitro studies in cell lines and the high-Ca2+ CA (made with 40 mM Ca2+) used in mouse models—in terms of protein corona formed with different concentrations of serum in vivo and in vitro. The 10-fold more Ca2+ in high-Ca2+ CA helped produce enough particles in an injectable volume for in vivo delivery of therapeutics. Both formulations made particles of similar size, but their composition differed slightly in terms of Na and Mg content. In serum-containing media, the size of the particles was dependent on the serum concentration. The protein corona around both formulations was almost similar and included albumin, fetuin, haemoglobin, and immunoglobulins. CA was not cytotoxic, and instead an increased expression of ribosomal machinery and glycolytic and cytoskeletal proteins was observed, which promoted translation, growth, and proliferation in cancer cells.