Harnessing Perfluorocarbon-Based nanocarriers for Rhodium(III) NHC complex Delivery: Synthesis, Characterization, and cytotoxicity evaluation

[Display omitted] •New highly fluorinated NHC rhodium(III) complexes were synthesized.•The complexes were incorporated into the core of artificial oxygen carriers (AOCs).•A theranostic nanocarrier system for fluorous NHC-metallodrugs was developed.•Rhodium(III)-loaded nanocarriers showed significant cytostatic potential. Perfluorocarbon-based nanoemulsions offer a promising platform for the delivery of poorly water‑soluble therapeutic agents while allowing for the tracking of nanocarriers biodistribution using 19F NMR and ultrasonography. In this study, highly fluorinated rhodium(III) complexes with an N–heterocyclic imidazolidene carbene ligand bearing polyfluoralkyl tag were synthesized and incorporated into the perfluorodecalin core of water–compatible albumin–derived perfluorocarbon–based nanocarriers to enable delivery of this hydrophobic cytostatic to cells in an aqueous environment. The formation of rhodium(III) complexes was confirmed by NMR spectroscopy, elemental analysis (EA) and mass spectrometry (MS). The fluorophilicity of the complexes, crucial for the preparation of rhodium–filled perfluorocarbon–based nanocarriers, was determined by the partition coefficient, indicating strong affinity for fluorinated environments (fi = 1.8–2.5). To demonstrate a broad field of applications, the rhodium–loaded nanocarriers were prepared directly in three different cell culture media (DMEM, RPMI1640 and ECM), exhibiting small droplet sizes ( 200 nm) and negative zeta potentials, indicating good physical stability and bicompatibility. Minimal changes in particle size distribution after three weeks of storage confirm their long–term stability. Furthermore, cytotoxicity of the rhodium-loaded nanocarriers, crucial for use as cytostatic, was investigated on renal carcinoma cells indicating a significant increase in lactate dehydrogenase (LDH) levels and cell death. These findings underscore the successful development of an effective drug delivery system of hydrophobic fluorous NHC rhodium(III) complexes for potential use as cytostatic drug in biological environments.