Studies On DNA Mediated-Functioalized Mesoporous Silica Nanoparticles For Controlled Release And Biosensing

With the development of nanotechnology, various nanomaterials with excellent structure and properties have been prepared for life sciences, pharmacy, medicine, and chemical industry, in particular, new technique and innovation promote the development and application of nanomaterials. Recently, mesoporous silica nanoparticle（MSN）, due to its order mesoporous structure, high surface area, large mesoporous volumn, ease of functionalization, has been developed as drug vehicles with good biocompatibility, which shows broad application in stimuli-responsive controlled release and biosensors. From the research point of view, two design principles have been developed to fabricate gatekeepers of MSN. As the great majority of the reported routes, the capping agents are covalently immobilized on the MSNs surface via a stimuli-labile linkage, such as redox-dependent disulfide bond. Despite their promise, these systems still have important limitations with respect to practical application. For example, preparation, derivation and attachment of the capping agents to MSN surface are sophisticated and involve tedious and intricate steps. Additionally, uncapping the capped agent by chemical reaction may not only require long reaction process, but also cause complications in the human body. An alternative way is non-covalent combination of the capping agents on the MSN surface by electrostatic force or host-guest interaction. However, the relatively weak interaction between the capped agents and MSN makes the combinations unstable in complex biological settings, and undesirable leakage of the drug during the course of delivery. In addition, though tracking drug delivery and monitoring drug release can provide reference for on-demand delivery and individual-based treatment, there is a few relative research works. Consequently, MSN is employed as the nanovehicles to design intracellular self-responsive visually controlled drug delivery systems and a new method is developed for in vivo hydrogen peroxide detection via Fenton reaction. The main research aspects are as follow:1) Study on the mesoporous silica nanoparticles modified with DNA-guided in situ growth of controlled silver nanoparticlesA kind of glutathione（GSH）-mediated controlled released systems based on MSN functionalized with rich-cytosines derivatives is designed and demonstrated. In the system, silver nanoparticles（Ag NPs） via DNA-templated in situ growth, as ideal gatekeeper, show good bioresponsiveness of biothiol by specific S-Ag reaction that allows to rapid release of the loaded drug molecules without formation of toxic components, which is also different from the existing methods that rely on chemical cleavage of a disulfide bond connecting the capped agent and carrier vehicles. Furthermore, by in situ formation of the capping agents, the size, shape and amount of the capping agents are easily modulated so that the gated systems possess tunable-controlled properties to meet different degrees of external stimuli.2) A visual controlled and targeted release system using DNA-guided and GSH-stimulated mesoporous silica nanoparticlesBased on the above work, a traceable and tumor-targeted intracellular drug release nanocontainer is obtained by in situ growth of Ag NPs on the surfaces of MSN using a DNA-templated process. After being functionalized with aptamer and PEG on the outer shell of the Ag NPs, the targeted nanocontainers are delivered into targeted cells by aptamer-mediated recognition and endocytosis. Additionally, drug release from the nanopores is achieved by selective GSH-triggered dismantle of the Ag NPs, and the concurrent fluorescence change allows real-time monitoring of drug release efficacy and facile visualization of in vivo delivery events. Moreover, the GSH-responsive process presents an improvement in the cell-specific drug release and chemotherapeutic inhibition of tumor growth.3) A mesoporous silica nanoparticles-based nanosensor by Fenton chemistry for In vivo imaging of hydrogen peroxideFor the limitation on Fenton chemistry-based sensor for hydrogen peroxide（H₂O₂） in the buffer or cell lysis, a “bio-gate” is formulated from MSN entrapped with ferrocene（Fc） and coated with self-assembly complex of fluorescently labeled DNA and perylene derivative（PTAD）. The bio-gate can image H₂O₂ within living animals through a two-step process containing hydroxyl radical（×OH） generated from Fc-catalytic conversion of H₂O₂, and subsequently oxidative cleavage of DNA, which makes disruption of FRET and further an increase in fluorescence, affording a unique technology for in situ detection and imaging of physiologic H₂O₂ fluxes in living system.4) A traceable and H₂O₂-stimulated drug delivery systems with self-assemble complex of fluorescent DNA and PTAD on the mesoporous silica nanoparticlesBased on the above work, due to the special binding of aptamer to receptor overexpressed on the surface of the cells, a traceable and tumor-targeted intracellular drug release nanocontainer is obtained by in situ self-assemble of fluorescent aptamer and PTAD on the surfaces of MSN. Additionally, drug release from the nanopores is achieved through a two-step process as aforementioned, leading to the enhancement of the fluorescence. The concurrent fluorescence change allows real-time monitoring and facile visualization of in vivo drug release events. Due to the targeted efficacy of the complexs of the aptamer and PTAD, the nanocontainers are delivered into targeted cells by receptor-mediated recognition and endocytosis. Moreover, the H₂O₂-responsive process presents an improvement in the cell-specific drug release and chemotherapeutic inhibition of tumor growth.