Citric acid functionalized silane coupling versus post-grafting strategy for dual pH and saline responsive delivery of cisplatin by Fe3O4/carboxyl functionalized mesoporous SiO2 hybrid nanoparticles: A-synthesis, physicochemical and biological characterization

Abstract

Synthesis of monodisperse carboxylic acid-functionalized magnetic mesoporous silica nanoparticles is performed by either two-step sol-gel process or post-grafting using citric acid modified isocyanate silane coupling agent (MMSN-NCO-CA) or succinic anhydride modified magnetic mesoporous silica (MMSN-NH-SA). Morphology, structure and magnetic properties of bare and mesoporous silica coated Fe3O4 core were studied using various techniques such as FTIR, VSM, TEM, FESEM, XRD and N2 adsorption–desorption isotherms (BET). Cisplatin (cis-Pt) adsorption isotherms and its release profile in various media were investigated by ICP-OES. MMSN-NCO-CA with mean particle size 107 nm had lower surface area (87.5 m2/g) and larger pore size (6.9 nm) in comparison with MMSN-NH-SA (respective values of 151.2 m2/g and 3.5 nm). cis-Pt loading into particles followed a saturable adsorption with respect to the drug to particle mass ratios. More sustained release of cis-Pt was observed for MMSN-NCO-CA, though both nanoparticles exhibited a pH- and saline concentration-dependent drug release. In addition, general and cis-Pt specific cytotoxicity were examined by MTT assay in MDA-MB-231 breast cancer cell line, and to further detect apoptosis, acridine orange/ethidium bromide dual cell staining was investigated by fluorescence microscopy. In-vitro anti-tumor efficiency of cis-Pt loaded MMSN-NCO-CA and MMSN-NH-SA were similarly enhanced in comparison to free cis-Pt; however, more specific apoptotic death occurred for cis-Pt loaded MMSN-NCO-CA. Therefore, the as-synthesized citric acid functionalized core-shell magnetic mesoporous hybrid nanoparticles could be used as a promising drug carriers for cancer therapy in-vivo.