Nanodiamond as a Vector for siRNA Delivery to Ewing Sarcoma Cells

Alhaddad, Anna; Adam, Marie-Pierre; Botsoa, Jacques; Dantelle, Géraldine; Perruchas, Sandrine; Gacoin, Thierry; Mansuy, Christelle; Lavielle, Solange; Malvy, Claude; Treussart, François; Bertrand, Jean-Rémi

doi:10.1002/smll.201101193

Cited by 217 publications

(199 citation statements)

References 49 publications

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“…[16][17][18] In order to synthesize ND-based gene carriers, the aim is to generate a cationic surface, which can electrostatically interact with anionic genetic materials. 19,20 Such examples are noncovalent functionalization with polymers like polyethylenimine 21 and covalent conjugation of derived organic moieties like triethylammonium groups. 22 Introducing protonable biomolecules, including amino acids, peptides, and proteins, on the ND surface is a novel approach for functionalization.…”

Section: Introductionmentioning

confidence: 99%

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

Alwani¹,

Kaur²,

Michel³

et al. 2016

IJN

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Purpose Nanodiamonds (NDs) are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND) in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. Methods lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA) was also analyzed using flow cytometry. Results Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed good stability, remaining under 100 nm throughout the testing period. A positive zeta potential of >+20 mV indicated a preservation of surface charges. Size distribution and zeta potential changed for lys-NDs after incubation with blood serum, suggesting an interaction with biomolecules, mainly proteins, and a possible formation of a protein corona. Cellular internalization of lys-NDs was confirmed by various techniques such as confocal microscopy, soft X-ray spectroscopy, and flow cytometry. Conclusion This study establishes that dispersion of lys-NDs in aqueous medium maintains long-term stability and also provides evidence that lysine functionalization enables NDs to interact effectively with the biological system to be used for RNAi therapeutics.

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Section: Introductionmentioning

confidence: 99%

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

Alwani¹,

Kaur²,

Michel³

et al. 2016

IJN

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“…Specific inhibition of EWS/Fli-1 gene expression was also observed at the mRNA and protein levels in a serum-containing medium. 76,77 This promising data warrant a further study about the in vivo system to test its efficiency of tumor treatment.…”

Section: Nanodelivery Of Gene Therapies For Bone Diseasesmentioning

confidence: 82%

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

Wu²,

Chen³

et al. 2013

IJN

159

111

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Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.

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“…Lately, a new kind of polymer named "chargereversal" has appeared, whose main property is the ability to change their charge as a function of pH, being positive at neutral pH and negative in acidic conditions. One of the best examples is PAH-Cit, which is also effective in reducing the possible cytotoxicity induced by highly positive species [29,108,109].…”

Section: Ionic Approachmentioning

confidence: 99%

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

et al. 2015

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RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to downregulate specific gene expression in diseased cells; opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the "do's and dont's" of the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 2 inorganic RNAi nanomaterials developed in the last 15 years and the different strategies employed are compared and scrutinized, offering important suggestions for the next 15. *Manuscript Click here to view linked References

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Nanodiamond as a Vector for siRNA Delivery to Ewing Sarcoma Cells

Cited by 217 publications

References 49 publications

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

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