Freeze-dried cationic calcium phosphatenanorods as versatile carriers of nucleic acids (DNA, siRNA)

Klesing, Jan; Chernousova, Svitlana; Epple, Matthias

doi:10.1039/c1jm13502c

Cited by 66 publications

(43 citation statements)

References 36 publications

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“…In contrast to Lipofectamine, calcium phosphate nanoparticles can be freeze-dried for long term storage and still keep their biological function when redispersed, 33 and they can also be labelled with cell-targeting moieties like antibodies, 49 proteins, 50 or peptides, 32 opening the possibility for a cell-specific downregulation of inflammatory markers in vivo. By introducing anti-TNF-a siRNA into the cells, the expression of the cytokine was strongly downregulated, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…24 The rise in osmotic pressure supports the escape of the nucleic acids into the cytosol. 33 Based on these promising results, we have prepared calcium phosphate nanoparticles which are loaded with siRNA against TNF-a to reduce its expression in stimulated MODE-K cells. 28,29 Furthermore, as mineral in human hard tissue (bone and teeth), calcium phosphate is a biocompatible and biodegradable compound.…”

Section: Introductionmentioning

confidence: 99%

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Gene silencing of the pro-inflammatory cytokine TNF-α with siRNA delivered by calcium phosphate nanoparticles, quantified by different methods

et al. 2015

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The pro-inflammatory cytokine TNF-a was silenced by treating MODE-K cells with triple-shell calcium phosphate nanoparticles. These consisted of a core of calcium phosphate, followed by a shell of siRNA, then a shell of calcium phosphate to protect the siRNA from nucleases and finally a shell of poly(ethyleneimine) for colloidal stabilization and to give the particles a positive charge. First, the gene silencing efficiency was demonstrated with HeLa-eGFP cells and determined by manually counting the green fluorescent cells, by quantitative FACS analysis of the green fluorescence per cell, and by qPCR at the RNA level. Cell counting gave the highest degrees of eGFP expression, but FACS and qPCR gave more accurate data as they are not probing the cell colour (green or not green) only as yes/no property. This was transposed to the inflammatory relevant mouse cell line MODE-K that was previously stimulated with LPS to induce the expression of TNF-a. By application of the nanoparticles, the TNF-a expression was reduced almost to the original level, as shown by qPCR. Thus, calcium phosphate nanoparticles are well suited to reduce inflammatory reactions by silencing the corresponding cytokines, e.g. TNF-a.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gene silencing of the pro-inflammatory cytokine TNF-α with siRNA delivered by calcium phosphate nanoparticles, quantified by different methods

et al. 2015

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“…The toxicity of PEI partly comes from its limited biodegradability [35]. Klesing et al [36] functionalized commercial hydroxyapatite nanorods with polyethyleneimine (PEI) and an average particle size of 190 nm without any agglomerates was obtained. In order to track the adsorption capacity of the HA-PEI nanorods, varying amounts of DNA was added to the dispersion and the dispersion stability was monitored by dynamic light scattering.…”

Section: The Use Of Calcium Phosphate Nanoparticles For Gene Therapymentioning

confidence: 99%

“…Nevertheless, some successfully in vitro siRNA delivery applications were reported by using PEI as a surface modifier. Klesing et al [36] developed a cationic nucleic acid delivery system based on hydroxyapatite nanorods functionalized with a layer of PEI. For gene silencing, HeLa-EGFP cell line (a genetically modified transformed cervix epithelial cell line expressing the enhanced green fluorescent protein, EGFP) was used.…”

Section: The Use Of Calcium Phosphate Nanoparticles For Gene Silencingmentioning

confidence: 99%

Gene Delivery by Hydroxyapatite and Calcium Phosphate Nanoparticles: A Review of Novel and Recent Applications

Bakan¹

2018

Hydroxyapatite - Advances in Composite Nanomaterials, Biomedical Applications and Its Technological Facets

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Gene therapy is a targeted therapy which can be used in the treatment of various acquired and inherited diseases. Inhabitation of a gene function, restoring or improving a gene, or gaining a new function can be achieved by gene therapy strategies. The most crucial step in this therapy is delivering the therapeutic material to the target. Nanosized calcium phosphates (CaPs) have been considered as promising carriers due to their excellent biocompatibility. In this chapter, the delivery of DNA, siRNA, and miRNA by using CaP nanocarriers were compiled in detail and the main parameters which can affect the carrier properties and thus the gene transfer efficiency were also discussed.

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“…In such studies, a green fluorescent proteinencoding reporter plasmid combined with different carriers was normally used, such as calcium-doped organosilicate nanoparticles, 66 calcium phosphate nanoparticles, 67 argininefunctionalized hydroxyapatite nanorods, 68 or polymers. 69 The alternative approach, an application of nanoparticles as oligonucleotide (eg, small interfering ribonucleic acid [siRNA]) carriers, was also effective in other studies, using gold, 70 calcium phosphate, 71 and cationic polymer/lipid TransIT-TKO ® nanoparticles.…”

Section: Gene Deliverymentioning

confidence: 99%

Nanoparticles and their potential for application in bone

Tautzenberger¹,

Kovtun²,

Ignatius³

2012

IJN

162

137

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Abstract:Biomaterials are commonly applied in regenerative therapy and tissue engineering in bone, and have been substantially refined in recent years. Thereby, research approaches focus more and more on nanoparticles, which have great potential for a variety of applications. Generally, nanoparticles interact distinctively with bone cells and tissue, depending on their composition, size, and shape. Therefore, detailed analyses of nanoparticle effects on cellular functions have been performed to select the most suitable candidates for supporting bone regeneration. This review will highlight potential nanoparticle applications in bone, focusing on cell labeling as well as drug and gene delivery. Labeling, eg, of mesenchymal stem cells, which display exceptional regenerative potential, makes monitoring and evaluation of cell therapy approaches possible. By including bioactive molecules in nanoparticles, locally and temporally controlled support of tissue regeneration is feasible, eg, to directly influence osteoblast differentiation or excessive osteoclast behavior. In addition, the delivery of genetic material with nanoparticulate carriers offers the possibility of overcoming certain disadvantages of standard protein delivery approaches, such as aggregation in the bloodstream during systemic therapy. Moreover, nanoparticles are already clinically applied in cancer treatment. Thus, corresponding efforts could lead to new therapeutic strategies to improve bone regeneration or to treat bone disorders.

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Freeze-dried cationic calcium phosphatenanorods as versatile carriers of nucleic acids (DNA, siRNA)

Cited by 66 publications

References 36 publications

Gene silencing of the pro-inflammatory cytokine TNF-α with siRNA delivered by calcium phosphate nanoparticles, quantified by different methods

Gene silencing of the pro-inflammatory cytokine TNF-α with siRNA delivered by calcium phosphate nanoparticles, quantified by different methods

Gene Delivery by Hydroxyapatite and Calcium Phosphate Nanoparticles: A Review of Novel and Recent Applications

Nanoparticles and their potential for application in bone

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