Human Serum Albumin as a Smart Nanocarrier for [RuNO(CQ)(POA)Cl] Isomeric Complexes: Structural, Photodynamic, and Antitumor Activity Insights

Human serum albumin (HSA) is a natural and non-immunogenic nanocarrier with multifunctional binding pocket for various small bioactive molecules. Hereby, four [RuNO(CQ)(POA)X] (Ru 1-4) complexes with different configurations were synthesized, where CQ is 5-Cl-7-I-8-hydroxyquinoline, POA is 2-Pyrazinecarboxylic acid, and X is Cl or I. The -I group was transferred from the CQ ligand to the metal center Ru to form Ru-1 and 3 during the reaction process. The detailed binding modes and dynamic interactions of Ru 1-4 with HSA were investigated and clarified through analysis of the structures of the complex adducts. A subtle structural change in conformation and the substituted group leads to different recognition and binding modes with HSA for Ru 1-4. Both the complexes and their HSA complex adducts showed higher cytotoxicity against cancer cells, activating the mitochondrial-mediated endogenous pathway to induce apoptosis in HeLa cells and arresting the cell cycle at the S phase. The HSA complex adducts and photo irradiation slightly enhanced the antiproliferative activity against tumor cells. Notably, the complexes showed relatively low toxicity to developing zebrafish embryos. The studies offer insights into the interactions between metal complexes and HSA to design more effective protein-based drug delivery systems.

Abstract from PubMed (PMID 43004699). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.