Construction And Antitumor Application Of Multifunctional Mesoporous Silica Nanoparticle-based Nanocarrier

Nanocarriers are able to prolong the half-life of drug systemic circulation, enhance the accumulation of durg in tumor site and achieve the gole of targeted delivery thus to reduce systemic toxicity. On the above basis, combination of target, therapic and imaging functions on one nanocarrier to construct multifunctional nanocarrier, which meets the diverse demands in clinical applications, has become the next important direction of nanocarriers. As a kind of inorganic nanomaterial, mesoporous silica(MS), which offers several unique properties, such as high specific surface area, tunable pore size, large pore volume, easy to surface modification, good chemical stability and biocompatibility, ha s been widely applied as an important nanocarrier. So far, more and more researches focuse on stimuli-responsive controlled drug release systerm. There have been many reports on mesoporous silica based stimuli-response drug delivery system. However, for the aspects such as controlling drug leakage during circulation, improving target specificity and the combination of multiple therapeutic methods, there are still much to be done. In this paper, multifunctional nanocarrier was constructed based on mesoporous silica nanoparticles. The contents of this paper are as follows:(1)Fenton reaction-based multifunctional mesporous slica nanoparticles for imaging and targeted therapy of cancer cellsIn this chapter, ferrocenecarboxylic acid and a rhodamine-based Fe3+ probe were co-loaded into mesoporous silica nanoparticles. ?-cyclodextrin was served as gate keeper for its excellent biocompatibility. After which, RGD peptide was non-covalent incorporated to serve as target moieties. According to this design, mesoporous silica was functioned as a nano-reactor, in which ferrocenecarboxylic acid catalyzed endogenous hydrogen peroxide of cancer cells to generate highly cytotoxic hydroxyl radical through fenton reaction. The hydroxyl radical destroyed DNA in cancer cells and served as therapeutic agent. On the other hand, ferrocene carboxylic acid was oxidized to ferrocenium carboxylic acid which could coordinate with Fe3+probe to induce great enhance of fluorescence of the probe. In this way, combining imaging and targetded therapy of cancer cells together.(2) Silver nanoparticle gated, mesoporous silica coated gold nanorods: low premature release and multifunctional cancer theranostic platformIn this chapter, the photothermal modality of Au NRs and the high drug payload and excellent biocompatibility of mesoporous silica were combined together. Mesoporous silica coated gold nanorod(Au NR@MS) was synthesized through modified sol-gel method. The mesoporous channels were loaded with model photosensitizer TMPy P4. The surface of Au NR@MS was modified with single stranded DNA, after which silver nanoparticles were formed in situ on the DNA template to serve as the gatekeeper, then AS1411 aptamer was functionalized as the target moieties, thus formed a multifunctional cancer theranostic platform. TMPy P4 was quenched by gold nanorod before reaching target cells. After internalization, glutathione which presented high concentration within the cytosol, could form ultrastable Ag-S bonds with Ag NPs which made Ag NPs separated from DNA template, and released the photosensitizer. The released photosensitizer recoverd its activity and could efficiently produced singlet oxygen when irradiated by exciting light. Coupled with photothermal effect of gold nanorod, this theranostic platform could destroy cancer cells efficiently.