PH-responsive composite nanomaterial engineered from silica nanoparticles and luminescent mitochondrion-targeted Pt(II) complex as anticancer agent

Abstract

The present work introduces a pH-dependent adsorption of water-soluble Pt(II) complex with diimine and alkynylphosphonium ligands ([Pt]2+) onto a surface of silica nanoparticles (SN-OH) as a strategy to develop a carrier function with an acidification-driven release of the complex. The adsorption of the complex onto a negatively charged silica surface shifts the equilibrium between dimeric and monomeric complex forms. The surface loading of [Pt]2+ is efficient at pH 7.0, and the acidification to pH 4.5 triggers the complex release. The interaction of [Pt]2+ with bovine serum albumin (BSA) influences the cell internalization and intracellular pathway of the complex, as well as the formation of the [Pt]2+-loaded SN-OH protein corona. The cytotoxicity data for the series of cancer and normal cell lines reveal the loading of [Pt]2+ into SN-OH as an efficient route for lower cytotoxicity and greater anticancer specificity of the nanoparticles compared to the complex. The flow cytometry and confocal microscopy methods reveal similarities in the cell internalization and intracellular pathway of [Pt]2+ and the [Pt]2+-loaded nanoparticles. The mitochondrial localization of [Pt]2+ and the [Pt]2+-loaded SN-OH does not cause noticeable changes in the membrane potential of mitochondria, and the cytotoxicity of [Pt]2+ in both forms is due to a non-apoptotic mechanism of cell death. Both the cytotoxicity and increased anticancer specificity of nanoparticles are associated with their carrier function, which is more pronounced in cancer cells with overdeveloped lysosomal compartments compared to normal ones.