High-yield fabrication and properties of 1.4 nm nanodiamonds with narrow size distribution

Stehlík, Štěpán; Varga, M.; Ledinský, Martin; Miliaieva, Daria; Kozak, Halyna; Skákalová, Viera; Mangler, Clemens; Pennycook, Timothy J.; Meyer, Jannik C.; Kromka, Alexander; Rezek, Bohuslav

doi:10.1038/srep38419

“…Indeed, nanoparticles smaller than 6-8 nm have been already reported to be filtered at the glomeruli level [18,19]. In this respect, detonation ND with primary size included between 3 and 8 nm and even smaller [29] are good candidates for such elimination. For this study, we prepared radioactive tritiated DND to be able to trace these ultra-small particles after injection to mice.…”

Section: Discussionmentioning

confidence: 96%

Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution

Claveau

¹

,

Nehlig

²

,

Garcia‐Argote

³

et al. 2020

View full text Add to dashboard Cite

Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adults due in the vast majority to the EWS-FLI1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-FLI1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA. polymers or dendrimers [5]), inorganic (e.g., metallic nanoparticles such as gold, iron, titanium [4]) or mineral like clay [6], silica nanoparticles [7] and nanodiamonds [8,9]. Most inorganic nanocarriers present a good-to-high chemical stability; they have a low toxicity at therapeutic dose of the drug:carrier conjugate and are able to deliver their cargo compounds into cells. Nevertheless, the high stability of inorganic nanoparticles goes with the fact that they are not biodegradable, and for pharmacological applications, this can be a limiting factor. Therefore, for the safe development of these particles, it is crucial to determine their possible elimination pathways after administration and study how they are distributed in the body.Here, we report on the use of cationic detonation nanodiamonds (DND) for the delivery of siRNA directed against Ewing sarcoma (ES) junction oncogene EWS-FLI1 to ES tumor xenografted on mice. Ewing sarcoma is a rare bone and soft tissue cancer [10] which is caused in the vast majority of cases by the formation of EWS-FLI1 oncogene. To carry siRNA, DND surface needs to be modified to be able to bind negatively charged nucleic acids by electrostatic interactions. One strategy relies on cationic polymer coating of diamond surface, which is either done by electrostatic interaction [9,11] or by covalent grafting [12,13]. However, polymer coating may lead to the formation of large aggregates by crosslinking DND to other DND via polymer chains bridging. Another strategy, the one selected for this study, is based on the direct surface modification of DND using hydrogen gas combined with microwave plasma or with annealing method. Both hydrogenation methods were recently compared [14]. It was shown that after such reductive treatment, the hydrogenated DND (H-DND) can be dispersed in water, and acquire a positive surface charge characterized by a zeta potential of ...

show abstract

“…Indeed, nanoparticles smaller than 6-8 nm have been already reported to be filtered at the glomeruli level [18,19]. In this respect, detonation ND with primary size included between 3 and 8 nm and even smaller [24] are good candidates for such elimination. For this study, we prepared radioactive tritiated DND to be able to trace these ultrasmall particles after injection to mice.…”

Section: Discussionmentioning

confidence: 96%

Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution

Claveau¹,

Nehlig²,

Garcia‐Argote³

et al. 2020

Preprint

View full text Add to dashboard Cite

Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adult due in the vast majority to the EWS-Fli1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-Fli1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA.

show abstract

“…Higher brightness comes at the cost of larger particles. Currently, there have been many attempts to decrease size as well as to increase brightness …”

Section: Discussionmentioning

confidence: 99%

Nanodiamonds and Their Applications in Cells

Chipaux

¹

,

Laan

²

,

Hemelaar

³

et al. 2018

Small

View full text Add to dashboard Cite

Diamonds owe their fame to a unique set of outstanding properties. They combine a high refractive index, hardness, great stability and inertness, and low electrical but high thermal conductivity. Diamond defects have recently attracted a lot of attention. Given this unique list of properties, it is not surprising that diamond nanoparticles are utilized for numerous applications. Due to their hardness, they are routinely used as abrasives. Their small and uniform size qualifies them as attractive carriers for drug delivery. The stable fluorescence of diamond defects allows their use as stable single photon sources or biolabels. The magnetic properties of the defects make them stable spin qubits in quantum information. This property also allows their use as a sensor for temperature, magnetic fields, electric fields, or strain. This Review focuses on applications in cells. Different diamond materials and the special requirements for the respective applications are discussed. Methods to chemically modify the surface of diamonds and the different hurdles one has to overcome when working with cells, such as entering the cells and biocompatibility, are described. Finally, the recent developments and applications in labeling, sensing, drug delivery, theranostics, antibiotics, and tissue engineering are critically discussed.

show abstract

High-yield fabrication and properties of 1.4 nm nanodiamonds with narrow size distribution

Cited by 74 publications

References 53 publications

Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution

Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution

Delivery of siRNA to Ewing Sarcoma Tumor Xenografted on Mice, Using Hydrogenated Detonation Nanodiamonds: Treatment Efficacy and Tissue Distribution

Nanodiamonds and Their Applications in Cells

Contact Info

Product

Resources

About