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Metallic nanoparticles, preparation and uses thereof

A metal nanoparticle, nanoparticle technology, applied in the fields of wave energy or particle radiation treatment materials, X-ray/γ-ray/particle irradiation therapy, medical preparations containing active ingredients, etc., can solve the problem of not providing accurate quantitative dose enhancement coefficients. , No research on the size of nanoparticles, etc., to achieve amazing and efficient therapeutic effects

Active Publication Date: 2012-05-23
NANOBIOTIX SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Zhang et al. (Biomed Microdevices (2009), 11:925-933) provided computer data (Monte carlo simulation model), which confirmed that gold nanoparticles can enhance the effective dose of radiation, but did not study the effect of nanoparticle size on this dose enhancement. influences
This literature mentions Hainfeld nanoparticles with a diameter of 1.9 nm in the context of radiotherapy (see right column on page 930), but does not provide results that could help to accurately quantify the dose enhancement factor in biological systems, especially humans (see Montenegro et al., J.Phys.Chem.A.2009, 113, 12364-12369: "Monte Carlo Simulations and Atomic Calculations for Auger Processes in Biomedical Nanotheranostics" ))

Method used

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  • Metallic nanoparticles, preparation and uses thereof
  • Metallic nanoparticles, preparation and uses thereof
  • Metallic nanoparticles, preparation and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0222] Example 1: Synthesis and Physicochemical Characterization of Gold Nanoparticles with Different Sizes

[0223] Gold nanoparticles were obtained by reducing gold chloride with sodium citrate in aqueous solution. Protocol adapted from G. Frens Nature Physical Science 241 (1973)21.

[0224] In a typical experiment, the HAuCl 4 The solution was heated to boiling. Sodium citrate solution was then added. The resulting solution was kept boiling for a further 5 minutes.

[0225] By carefully adjusting the ratio of citrate to gold precursor, the nanoparticle size was adjusted from 15 to 105 nm (see Table 1).

[0226] The gold nanoparticle suspension thus prepared was then concentrated using an ultrafiltration unit (Amicon stirred cell model 8400 from Millipore) using a 30 kDa cellulose membrane.

[0227] Finally, the resulting suspension was filtered under a laminar flow hood through a filter with a cut-off of 0.22 μm (PES membrane from Millipore) and stored at 4°C.

[02...

Embodiment 2

[0237] Example 2 : Effect of Gold Nanoparticle Size on In Vitro Potency at Constant Gold Concentration at Cellular Level (Clonogenic Survival Assay)

[0238] Program

[0239] To investigate how gold nanoparticles (GNPs) internalized into or bound to cells (expressed hereinafter as gold concentration at the cellular level) enhance the radiation response, the inventors used a specific clonogenic survival assay as described below :

[0240] HT29 cells were treated at 20 000 cells / cm 2 density planks. GNPs were added to the medium at various gold concentrations in the μM range. After an incubation time between 1 hour and 24 hours, the cell supernatant was removed. Cells were then washed briefly with PBS to remove any GNP that was not attached to or internalized into the cells. Next, the present inventors performed trypsinization of cells and counted the number of cells using a hemocytometer.

[0241] For each condition, the inventors took samples from 100000 cells / mL up ...

Embodiment 3

[0272] Example 3: Effect of gold nanoparticle size on in vitro potency when the X-ray attenuating capacity of each tested gold nanoparticle is constant at the cellular level

[0273] Solution: X-ray attenuation measurement

[0274]Gold nanoparticles with different gold concentrations (expressed as [Au]g / L) were prepared in 200 μL tubes and placed on specially customized polystyrene racks.

[0275] μCT was performed using a General Electric Locus μCT system with anodic voltage and current of 50 KV and 450 μA, respectively.

[0276] Scans were performed using 90 μm isotropic resolution mode.

[0277] A small cylindrical target area was carefully placed in the 3D image above the center of each tube to measure the attenuation values ​​of the fluid-filled tubes containing the gold nanoparticle dispersion.

[0278] in conclusion

[0279] For sizes between 15nm and 105nm, similar X-ray attenuation was observed regardless of the size of the gold nanoparticles (see Figure 6A...

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Abstract

The present application relates to activable nanoparticles which can be used in the health sector, in particular in human health, to disturb, alter or destroy target cells, tissues or organs. It more particularly relates to nanoparticles which can generate a significantly efficient therapeutic effect, when exposed to ionizing radiations. The inventive nanoparticle is a metallic nanoparticle having, as the largest size, a size comprised between about 80 and 105 nm, the metal having preferably an atomic number (Z) of at least 25. The invention also relates to pharmaceutical compositions comprising a population of nanoparticles as defined previously, as well as to their uses.

Description

field of invention [0001] The present invention relates to activatable nanoparticles, which can be used in the field of health, especially human health, for disturbing, changing or destroying target cells, tissues or organs. More specifically, it relates to nanoparticles capable of surprisingly potent therapeutic effects when exposed to ionizing radiation such as X-rays, gamma-rays, radioisotopes and / or electron beams. The nanoparticles of the present invention are metal nanoparticles having a size between about 80 and about 105 nm as the largest dimension, and the metal preferably has an atomic number (Z) of at least 25. The invention also relates to pharmaceutical compositions comprising the populations of nanoparticles defined above and to their use. Background technique [0002] Various forms of radiation such as X-rays, gamma-rays, UV-rays, lasers, microwaves, electron beams and particle beams such as neutrons and protons have been used to treat cancer related problems...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61P35/00
CPCA61K41/0038A61P35/00A61P43/00A61N5/10A61N2005/1098
Inventor 劳伦特·莱维阿格尼丝·波迪艾尔劳伦斯·保罗劳伦斯·马格奥勒拉
Owner NANOBIOTIX SA