Targeting of Porous Hybrid Silica Nanoparticles to Cancer Cells

Center for Functional Materials, Department of Physical Chemistry, Abo Akademi University, Porthansgatan 3-5, FI-2500 Turku, Finland.
ACS Nano (Impact Factor: 12.88). 02/2009; 3(1):197-206. DOI: 10.1021/nn800781r
Source: PubMed

ABSTRACT Mesoporous silica nanoparticles functionalized by surface hyperbranching polymerization of poly(ethylene imine), PEI, were further modified by introducing both fluorescent and targeting moieties, with the aim of specifically targeting cancer cells. Owing to the high abundance of folate receptors in many cancer cells as compared to normal cells, folic acid was used as the targeting ligand. The internalization of the particles in cell lines expressing different levels of folate receptors was studied. Flow cytometry was used to quantify the mean number of nanoparticles internalized per cell. Five times more particles were internalized by cancer cells expressing folate receptors as compared to the normal cells expressing low levels of the receptor. Not only the number of nanoparticles internalized per cell, but also the fraction of cells that had internalized nanoparticles was higher. The total number of particles internalized by the cancer cells was, therefore, about an order of magnitude higher than the total number of particles internalized by normal cells, a difference high enough to be of significant biological importance. In addition, the biospecifically tagged hybrid PEI-silica particles were shown to be noncytotoxic and able to specifically target folate receptor-expressing cancer cells also under coculture conditions.

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Available from: Jessica Rosenholm, Sep 26, 2015
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    • "The percentage of cells in G0/G1 phase, S phase, G2/M and sub-G1 phase was analyzed using BD CellQuest Pro™ software. In order to identify the apoptotic cells a selected portion of the cells cycle, sub-G0/G1 phase was determined as a measure of nuclear fragmentation [32] [45]. "
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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.
    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 · 3.38 Impact Factor
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    • "Nanoparticle based targeted drug delivery systems hold great promise for cancer therapy because of their targeting functions [1], sustained drug release profiles [2], reduced side effects [3], and the ability to overcome multidrug resistance (MDR) [2] [4]. A variety of materials have been exploited to meet different therapeutic needs, many with great potential for topical delivery [5] [6] [7]. "
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    ABSTRACT: Hollow mesoporous silica nanoparticles were successfully fabricated and functionalized with appropriate silanes. After modifications, amine, carboxyl, cyano, and methyl groups were grafted onto the nanoparticles and all functionalized hollow mesoporous silica nanoparticles maintained a spherical and hollow structure with a mean diameter of ~120 nm and a shell thickness of ~10 nm. The loading capacity of the hollow mesoporous silica nanoaprticles to the anticancer drug, 5-fluorouracil, can be controlled via precise functionalization. The presence of amine groups on the surface of nanoparticles resulted in the highest loading capacity of 28.89%, due to the amine functionalized nanoparticles having a similar hydrophilicity but reverse charge to the drug. In addition, the change in pH leads to the variation of the intensity of electrostatic force between nanoparticles and the drug, which finally affects the loading capacity of amine functionalized hollow mesoporous silica nanoparticles to some extent. Higher drug loading was observed at pH of 7.4 and 8.5 as 5-fluorouracil becomes more deprotonated in alkaline conditions. The improved drug loading capacity by amine functionalized hollow mesoporous silica nanoparticles has demonstrated that they can become potential intracellular 5-fluorouracil delivery vehicles for cancers.
    Journal of Nanomaterials 03/2015; 2015:1-9. DOI:10.1155/2015/872035 · 1.64 Impact Factor
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    • "Mansoori et al. (2010) have reported the synthesis of a folate-conjugated gold nanoparticle to study the tissue distribution and endocytosis of cancer cells expressing high levels of FRs. In a similar work, Rosenholm et al. (2009) evaluated the cellular uptake of mesoporus particles covalently functionalized with folates in cancer cells and cells non-overexpressing FRs. "
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    ABSTRACT: Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The surface analysis of PNT-FA indicated the presence of FA aggregates on the surface of PNTs. The covalent interaction between FA and self-assembled PNTs was further investigated using fluorescence microscopy, Raman and surface-enhanced Raman scattering (SERS) spectroscopies. The SERS experiments were performed on a large area silver-capped (diameter of 62 nm) silicon nanopillars with an approximate height of 400 nm and a width of 200 nm. The results showed that the PNT-FA synthesis procedure preserves the molecular structure of FA. The PNT-FA conjugate presented in this study is a promising candidate for applications in the detection and diagnosis of cancer or tropical diseases such as leishmaniasis and as a carrier nanosystem delivering drugs to malignant tumors that overexpress folate receptors.
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