Nanoparticles in Targeted Cancer Therapy: Mesoporous Silica Nanoparticles Entering Preclinical Development Stage

Rosenholm, Jessica M.; Mamaeva, Veronika; Sahlgren, Cecilia; Lindén, Mika

doi:10.2217/nnm.11.166

Cited by 238 publications

(171 citation statements)

References 55 publications

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“…Chemical design of nanoparticles offers control over bioavailability and biodistribution, but we still need to address the form and function relationships for any given administration. 3,4 The Notch signaling pathway is the key regulator of stem cells in development and tissue homeostasis, and is deregulated in inflammatory intestinal disease and colon cancer. 5,6 Clinical studies inhibiting Notch are focused on several types of cancers by mainly two approaches: use of antibodies against receptors and ligands, and…”

Section: Introductionmentioning

confidence: 99%

Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

Desai¹,

Prabhakar²,

Mamaeva³

et al. 2016

IJN

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Targeted delivery of drugs is required to efficiently treat intestinal diseases such as colon cancer and inflammation. Nanoparticles could overcome challenges in oral administration caused by drug degradation at low pH and poor permeability through mucus layers, and offer targeted delivery to diseased cells in order to avoid adverse effects. Here, we demonstrate that functionalization of mesoporous silica nanoparticles (MSNs) by polymeric surface grafts facilitates transport through the mucosal barrier and enhances cellular internalization. MSNs functionalized with poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and the targeting ligand folic acid in different combinations are internalized by epithelial cells in vitro and in vivo after oral gavage. Functionalized MSNs loaded with γ-secretase inhibitors of the Notch pathway, a key regulator of intestinal progenitor cells, colon cancer, and inflammation, demonstrated enhanced intestinal goblet cell differentiation as compared to free drug. Drug-loaded MSNs thus remained intact in vivo, further confirmed by exposure to simulated gastric and intestinal fluids in vitro. Drug targeting and efficacy in different parts of the intestine could be tuned by MSN surface modifications, with PEI coating exhibiting higher affinity for the small intestine and PEI–PEG coating for the colon. The data highlight the potential of nanomedicines for targeted delivery to distinct regions of the tissue for strict therapeutic control.

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Section: Introductionmentioning

confidence: 99%

Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

Desai¹,

Prabhakar²,

Mamaeva³

et al. 2016

IJN

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“…SiO 2 NPs are being proposed as new tools for imaging [23][24][25] and drug and biologic delivery (e.g., nucleic acidbased reagents and siRNA) [26][27][28][29][30]. SiO 2 NPs may exist in many different forms, including different crystallinity, morphology, and pore structure, with each form exhibiting unique characteristics [31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Viability and Proliferation Profiles on Macrophages Treated with Silica Nanoparticles In Vitro via Plate-Based, Flow Cytometry, and Coulter Counter Assays

Bancos

Tsai

Hackley

et al. 2012

ISRN Nanotechnology

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Nanoparticles (NPs) are known to interfere with many high-throughput cell viability and cell proliferation assays, which complicates the assessment of their potential toxic effects. The aim of this study was to compare viability and proliferation results for colloidal silica (SiO 2 NP; 7 nm) in the RAW 264.7 mouse macrophage cell line using three different techniques: plate-based assays, flow cytometry analysis, and Coulter counter assays. Our data indicate that CellTiter-Blue, XTT, and CyQuant plate-based assays show increased values over control at low SiO 2 NPs concentrations (0.001-0.01 g/L). SiO 2 NPs show little-to-no interference with flow cytometry and Coulter counter assays, which not only were more reliable in determining cell viability and proliferation at low concentrations in vitro, but also identified changes in cell granularity and size that were not captured by the plate-based assays. At high SiO 2 NP concentrations (1 g/L) all techniques indicated cytotoxicity. In conclusion, flow cytometry and Coulter counter identified new cellular features, and flow cytometry offered more flexibility in analyzing the viability and proliferation profile of SiO 2 NP-treated RAW 264.7 cells.

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“…33,34 Predominant excretion forms of silica nanoparticles in urine are known to be silicic acid or oligomeric silica species. 35,36 Thus, sodium or potassium silicic acid salts could be excreted from the organs with the urine. Furthermore, it seems that absorbed nanoparticles (about 6.6%-9.7%) are excreted by the urinary system.…”

mentioning

confidence: 99%

Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

An¹,

Lee²,

Kim³

et al. 2014

IJN

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Purpose The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods Silica nanoparticles of two different sizes (20 nm and 100 nm) were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict potential toxicological effects of silica nanoparticles on target organs.

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Nanoparticles in Targeted Cancer Therapy: Mesoporous Silica Nanoparticles Entering Preclinical Development Stage

Cited by 238 publications

References 55 publications

Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

Evaluation of Viability and Proliferation Profiles on Macrophages Treated with Silica Nanoparticles In Vitro via Plate-Based, Flow Cytometry, and Coulter Counter Assays

Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

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