Functionalization of Mesoporous Silica Nanoparticles for Targeting, Biocompatibility, Combined Cancer Therapies and Theragnosis

Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
Journal of Nanoscience and Nanotechnology (Impact Factor: 1.56). 04/2013; 13(4):2399-430. DOI: 10.1166/jnn.2013.7363
Source: PubMed


The advent of Nanotechnology has paved a way for improved disease treatment strategies, the most noteworthy being the mesoporous silica nanoparticles (MSNs) which have gained much recent attention in the field of cancer therapy and its diagnosis. The flaws of the current-day strategies can be overcome by this superior technology through its targeting ability in delivering drugs and image able agents specifically to the tumor sites. MSNs have unique biocompatibility features, its high surface area which contributes in large amount of drug loading and its facility to monitor size and shape of the nanoparticles are few of the positives which makes this technology an enormous asset for the field of Nanotechnology. This review paper is structured in such a way wherein we initially have discussed about the synthesis methods and various functionalization approaches for MSN followed by the different methods used for targeting cancer cells and the latest advances in controlled drug release. Some of the highlights of this review are the biocompatibility of MSNs, in vivo results of MSNs on cancer therapy. This review paper also shortly discuss about combined cancer therapies to overcome the challenges in current-day cancer treatment. Finally, we converge briefly on the recent advancements in the use of hybrid MSNs for obtaining multiple functions.

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Available from: Yaswanth Kuthati, May 26, 2015
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    • "To maximize the uptake, we used glucose moieties as affinity ligands, conjugated onto the surface of mesoporous silica nanoparticles (MSNs) for increasing the affinity toward cancer cells as compared to healthy cells. MSNs were chosen due to their characteristic suitability to carry, especially poorly water soluble, payload within their molecular-sized pores; as well as their flexible surface functionalization possibilities [19] [20] [21]. To take advantage of the latter and enable multivalent presentation of the sugar moieties on the MSN surface, a hyperbranched surface polymer was used as linker between the MSNs and glucose entities [22] and the internalization efficiency was compared to that of particles without this polymeric layer (Scheme 2). "
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    ABSTRACT: Cancerous cells have a rapid metabolism by which they take up sugars, such as glucose, at significantly higher rates than normal cells. Celastrol is a traditional herbal medicine known for its anti-inflammatory and anti-cancer activities. The poor aqueous solubility and lack of target selectivity of celastrol result in low therapeutic concentration of the drug reaching subcellular compartments of the target tissue, making it an interesting candidate for nanoparticulate delivery. The goal of this study was to utilize glucose as an affinity ligand decorated on mesoporous silica nanoparticles (MSNs), with the aim of delivering these celastrol-loaded MSNs with high specificity to cancer cells and inducing minimal off-target effects in healthy cells. MSNs were thus functionalized with sugar moieties by two different routes, either by conjugation directly to the MSN surface or mediated by a hyperbranched poly(ethylene imine), PEI layer; the latter to increase the cellular uptake by providing an overall positive surface charge as well as to increase the reaction sites for sugar conjugation. The effect of surface functionalization on the target-specific efficacy of the particles was assessed by analyzing the uptake in HeLa and A549 cells as cancer cell models, as compared to mouse embryonic fibroblasts (MEF) as a representative for normal cells. To this end a comprehensive analysis strategy was employed, including flow cytometry, confocal microscopy, and spectrophotometry. When the apoptotic effect of celastrol was evaluated, the anti-cancer activity of celastrol was shown to be significantly enhanced when it was loaded into the specifically designed MSNs. The particles themselves did not induce any toxicity, and normal cells displayed minimal off-target effects. In summary, we show that glucose-functionalized MSNs can be used as efficient carriers for targeted celastrol delivery to achieve specific induction of apoptosis in cancer cells.
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    • "The advent of nanotechnology has altogether revolutionized the field of drug delivery with a faster and more sensitive response than the conventional drug delivery vehicles with a very low to zero premature drug release, and also offered new targeting strategies for disease diagnosis and treatment . Among various nanomaterials studied inorganic-based drug delivery vehicles such as mesoporous silica nanoparticles (MSN), iron oxide nanoparticles, gold nanoparticles, fullerenes and carbon nanotubes (CNT) have brought new possibilities to this emerging field of research for controlled release of various cargos through surface functionalization (Liong et al., 2008; Kuthati et al., 2013; Zhang et al., 2014). Layered double hydroxides are one among this unique class of inorganic nanocontainers that have been intensively studied as drug delivery carriers since their arrival, due to their versatile features suitable for drug delivery which include high surface area, particle swelling property, memory effect, high anion exchange capacity and stable physicochemical properties (Costantino et al., 2012). "
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