Functionalized mesoporous silica nanoparticles for stimuli-responsive and targeted drug delivery
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 interesting results were 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 promoted the loading and delivery of the drug. The results were confirmed by in vitro drug delivery studies on Chinese hamster ovarian cells (CHO).
We further applied the magnetic mesoporous silica nanomaterial to develop a magnetically active nanocarrier for photosensitive delivery of camptothecin to cancer cells. The mesopores were loaded with the drug and the pore entrances were blocked by functionalized cadmium-sulfide nanoparticles through an o-nitrobenzyl-based photolabile linker. Upon irradiation with UV light the photolabile linker was cleaved which induced release of the anticancer drug. The cooperative anticancer effect of capping CdS nanoparticles and loaded camptothecin was demonstrated by in vitro viability studies on CHO cells, upon exposure of the cell cultures to low power UV light.
Finally, we constructed a mesoporous silica nanoparticle-based nanocarrier which was capable of delivering the mesopore-loaded molecules upon irradiation with visible light. The cargo molecules were entrapped inside the mercaptopropyl-functionalized mesopores of MSN by an S-coordinated metal complex. Upon exposure to visible light the metal-sulfur coordination bond is cleaved which allows release of the mesopore-loaded dye. Ligand substitution by nitrogen monoxide, imidazole and histidine was also shown to induce the release of cargo molecules, although with lower efficiency than with visible light.