Chelation of Cerium Ions with Fish Skin Collagen Peptides: Improving the in Vitro Stability and Bioavailability of Inorganic Cerium

Abstract

Purified fish skin collagen peptide (FSCP) was used to chelate cerium ions to prepare peptide-cerium chelates (FSCP-Ce) to improve their in vitro stability and cellular uptake for oral delivery. The study revealed that the primary chelation sites between FSCP and Ce3+ were located on the side chains of tryptophan, aspartic acid, glutamic acid, lysine and histidine. Notably, FSCP-Ce showed good in vitro stability, gastrointestinal digestive stability, and could reduce the cytotoxicity of cerium as well as promote cerium transport efficiency in the enterocyte. The endocytosis pathway results indicate that the main cellular transport pathways for FSCP-Ce are giant cytosol drinking and vesicle protein-dependent endocytosis, which adds multiple uptake pathways compared to CeCl3, and explains the higher bioavailability of the chelate during cellular uptake. This research establishes a basis for investigating peptide-cerium chelates as a new type of nutritional supplement, aiming to lower cerium toxicity while enhancing its bioavailability.

Keywords: Cerium, Collagen peptide, Chelation mechanism, In vitro stability, Cytotoxicity, Transcellular permeability