Amino acid-decorated mesoporous silica nanoparticles loaded with titanocene derivatives for targeted anticancer studies

Nanostructured materials possess promising potential for cancer therapy through precise adjustment of their functionalization and physicochemical attributes. This study primarily focuses on the synthesis and characterization of mesoporous silica nanoparticles (MSN) that are functionalized with titanocene dichloride (a therapeutic agent) and one of several amino acids-cysteine, captopril, penicillamine, or methionine-utilizing 3-aminopropyltriethoxysilane (AP) as a linker. This synthesis yielded four innovative metallodrug-functionalized nanostructured materials (MSN-AP-Cys-Ti, MSN-AP-Cap-Ti, MSN-AP-Pen-Ti, and MSN-AP-Met-Ti), meticulously characterized using diverse analytical techniques such as X-ray diffraction (XRD), X-ray fluorescence (XRF), diffuse reflectance ultraviolet-visible (DR UV-Vis), Fourier transform infrared (FTIR), solid-state nuclear magnetic resonance (NMR) spectroscopy, and transmission electron microscopy (TEM). The textural properties of the nanomaterials post-functionalization displayed slight modifications, confirming the successful integration of the therapeutic agents. Evaluation of cytotoxicity in the breast cancer cell line MDA-MB-231, with the healthy cell line Hek-293T as control via MTT assays, revealed the active nature of the functionalized silica-based materials. The viability of both cell lines indicated a concentration-dependent response to the materials. Among the tested systems, cysteine and captopril exhibited the highest activity concerning IC50 relative to material concentration. The enhanced biological activity of higher functionalized nanosystems suggests a favorable cell internalization facilitated by the amino acid fragment. Additionally, qualitative DNA binding studies hinted at potential DNA adsorption on the surface of the metallodrug-functionalized nanomaterials, forming DNA adducts where a strand of DNA covalently bonds to the metallodrug moiety. This was deduced from the hypsochromic shift in absorbance of the characteristic pi-pi* and n-pi* transitions in DNA, which occurred from 1.01 to 0.76 and 1.26-0.19 following drug (MSN-AP-Cap-Ti) interaction. Titanocene-functionalized nanostructured materials incorporating S-containing amino acids showed interesting structural features and a high cytotoxic potential against MDA-MB-231 triple-negative breast cancer cells linked to a synergistic incorporation of titanium centers through the amino acid. image