pH-Responsive Delivery of Anticancer Metal Complexes by Functionalized Mesoporous Silica-based Nanocarriers

Abstract

Mesoporous silica nanoparticles (MSN) exhibit high potential for constructing stimuli-responsive drug carriers for targeted cancer therapy. The material is characterized by high surface area (ca. 1000 m2 /g), various possibilities for surface functionalization, presence of mesopores (2-3 nm in diameter) and high biocompatibility. Drugs can be filled inside the mesopores or attached to the surface, while the surface of MSN can be specifically modified to allow the controlled release of the loaded drugs, triggered by a specific stimulus (change in pH, exposure to light, magnetic field, enzymes, etc.). Herein, novel cancer-targeting nanotherapeutics are developed based on MSN, containing therapeutic Ru(II)- and Ir(III)-coordination compounds covalently linked to the surface of MSN though an acidification-cleavable linker. This effect would enable targeted cancer treatment due to a weakly acidic environment of the extracellular matrix of tumor tissues, in comparison to the neutral pH of healthy tissues. Novel Ru(II) and Ir(III) coordination compounds are also synthesized, containing the same ligands that are attached on the surface of MSN, and their anticancer activity is also evaluated. The constructed series of novel nanomaterials and coordination compounds were characterized by scanning electron microscopy, thermogravimetric analysis, zeta potential and nitrogen sorption analyses, infrared spectroscopy, X-ray crystallography, and elemental analysis. The characteristics of prepared metal complexes and novel nanomaterials demonstrate high potential for their effective application in targeted cancer treatment, as determined by in vitro experiments on cancer cells.