Chelation of cerium (III) 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 Ce³⁺ to prepare peptide‑cerium chelate (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 (cerium-chelating capacity 75.32 mg/g). FSCP-Ce showed good in vitro stability, gastrointestinal digestive stability. Furthermore, this study demonstrated that the 1.32 mg/mL FSCP-Ce significantly increase cell viability (FSCP-Ce: 98.77 ± 1.56 % VS CeCl₃: 64.21 ± 1.92 %) and cerium absorption (FSCP-Ce: 57.59 ± 2.51 % VS CeCl₃: 27.29 ± 2.02 %) compared to 1 mg/mL CeCl₃. 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. This research establishes a basis for investigating peptide‑cerium chelate as a new type of nutritional supplement, aiming to lower cerium toxicity while enhancing its bioavailability.

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