Functionalized mesoporous silica nanoparticles for stimuli-responsive and targeted drug delivery

Abstract

Construction of functional supramolecular nanoassemblies has attracted great deal of attention in recent years for their wide spectrum of practical applications. Mesoporous silica nanoparticles (MSN) in particular were shown to be effective scaffolds for the construction of drug carriers, sensors and catalysts. Herein, we describe the synthesis and characterization of stimuli-responsive, controlled release MSN-based assemblies for drug delivery. First we report on devising a functional UV light responsive delivery system for doxorubicin, a widely used anticancer drug. A positively charged drug molecule is adsorbed on the surface of the MSN through charge interaction and hydrogen bonding with surface silanols. The surface of MSN contained nitroveratryl carbamate protected aminopropyl moieties which undergo deprotection upon irradiation with UV light. The drug delivery principle is based on charge repulsion between UV light-generated, positively charged propylammonium ions and positively charged doxorubicin molecules. Release of the drug also increases by lowering the pH from 7.4 to 6.4. This result is beneficial for selective drug delivery to tumor tissues, as most tumor tissues have low extracellular pH value. We then set forth to develop magnetic analogues of mesoporous silica nanoparticles in order investigate possibilities for magnetic field induced targeted drug delivery. A series of new materials was obtained with radial and hexagonal packing of the mesopores, containing magnetic nanoparticles inside the core of the mesoporous silicate framework. We monitored the ability of the magnetic materials to adsorb and deliver anticancer drugs, 9-aminoacridine and camptothecin, and an interesting result was obtained. If 9-aminoacridine was adsorbed on the magnetic materials, its release from the surface in PBS buffer was promoted if the silica surface was not functionalized with organic moieties. If camptothecin was adsorbed on the same materials, the presence of phenylethyl functional groups inside the mesopores