Carboxy‐thioether‐thiolato titanium–graphene oxide nanocomposite as drug delivery system for targeted cancer therapy: Design, characterization, bovine serum albumin binding study, and biological evaluation

Abstract

Carboxy-thioether-thiolato Ti (IV) complex (TiCTT) and its graphene oxide nanocomposite (GO-TiCTT) were prepared and characterized for the development of novel compounds with enhanced antibacterial and anticancer capabilities, and the loading ratio of TiCTT was found to be approximately 33.3%. Thermal studies and zeta potential revealed that GO-TiCTT is more stable than GO, whereas SEM and TEM revealed efficient TiCTT adsorption on the surface of GO. Various biophysical procedures were used to investigate the interactions of CTT, TiCTT, GO, and GO-TiCTT nanocomposite with bovine serum albumin (BSA). The results revealed that the intrinsic fluorescence quenching of BSA resulting from low concentrations was caused by the formation of stable BSA adducts via the binding interaction with BSA. The stable adduct had a stoichiometry of 1:1 and binding constants (K b ) in the order of 10 5 M1 at 310 K for CTT, TiCTT, and GO-TiCTT, indicating a very strong binding interaction with BSA. Based on the sign and magnitude of the free energy change (G#), it can be concluded that the binding process with BSA was spontaneous, with van der Waals force and hydrogen bonding interaction as the main interaction forces. A combined quenching process was observed at higher concentrations of these compounds. Using the stopped-flow technique, the TiCTT release behavior from the nanocomposite was investigated, and the GO-TiCTT system demonstrated pH-responsive and sustained drug release. Furthermore, when compared to GO, CTT, TiCTT, and GO-TiCTT nanocomposite demonstrated good antibacterial activity against both Gram-positive and Gram-negative bacteria. They also have higher cytotoxicity against HepG2 human liver cancer cells than CTT. The calculated BSA-binding constants matched the antimicrobial and cytotoxic results well. As a result, this research could lead to the development of a drug delivery system.

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms

“…Under this mechanism, the compounds work via the suppression of the chymotrypsin-like activity of the proteasome, specifically, chymotropsin β5 site, rather than the proteasome's other functions. 69,[206][207][208][209][210] Targeting this site has been reported as the most potent mechanism in triggering cancer cell death via apoptosis and this is currently an active area of research.…”