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: 1.34). 04/2013; 13(4):2399-430. DOI: 10.1166/jnn.2013.7363
Source: PubMed

ABSTRACT 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, results 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 performed by analyzing the uptake in HeLa and A549 cells as cancer cell models, as compared to mouse embryonic fibroblasts (MEFs) as 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 highly efficient carriers for targeted celastrol delivery to achieve specific apoptosis in cancer cells. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2015; 96. DOI:10.1016/j.ejpb.2015.07.009 · 4.25 Impact Factor
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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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    ABSTRACT: Functionalized Magnetic Iron Oxide Nanoparticles (FMIONPs) are being explored for the development of various biomedical applications, e.g., cancer chemotherapy and/or several other radiological or diagnostic purposes. However, the effects of these NPs per se on the central nervous system (CNS) injury or repair are not well known. This review deals with different aspects of FMIONPs in relation to brain function based on the current literature as well as our own investigation in animal models of CNS injuries. It appears that FMIONPs are innocuous when administered intravenously within the CNS under normal conditions. However, abnormal reactions to FMIONPs in the brain or spinal cord could be seen if they are combined with CNS injuries e.g., hyperthermia or traumatic insults to the brain or spinal cord. Thus, administration of FMIONPs in vivo following whole body hyperthermia (WBH) or a focal spinal cord injury (SCI) exacerbates cellular damage. Since FMIONPs could help in diagnostic purposes or enhance the biological effects of radiotherapy/chemotherapy it is likely that these NPs may have some adverse reaction as well under disease condition. Thus, under such situation, adjuvant therapy e.g., Cerebrolysin (Ever NeuroPharma, Austria), a suitable combination of several neurotrophic factors and active peptide fragments are the need of the hour to contain such cellular damages caused by the FMIONPs in vivo. Our observations show that co-administration of Cerebrolysin prevents the FMIONPs induced pathologies associated with CNS injuries. These observations support the idea that FMIONPs are safe for the CNS in disease conditions when co-administered with cerebrolysin. This indicates that cerebrolysin could be used as an adjunct therapy to prevent cellular damages in disease conditions where the use of FMIONPs is required for better efficacy e.g., cancer treatment.
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