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Chemical and Biological Characterizations of an Effective Bimodal Probe to Target Apoptosis
* 1, 2 , * 1
1  University of Mons, Departement of General, Organic and Biomedical Chemistry
2  University of Lyon-1, FENNEC Team, Lumière Matière Institute

Published: 02 November 2015 by MDPI in 1st International Electronic Conference on Medicinal Chemistry session ECMC-1
Abstract:

Introduction

AGuIX® nanoparticles are small platforms of polysiloxane recently developed for various applications of medical imaging. These nanoparticles contain on their surface several amine functions used for the fixation of DOTA ligands. Approximately 70 percents of these ligands are complexed with Gd3+ ions [1]. These paramagnetic platforms have a diameter less than 5 nm and a low transmetalation [2]. Different studies have been achieved in the biomedical domain, showing that they allow to combine multimodal and theranostic properties. A passive tumoral targeting has already been observed by EPR effect (Enhanced Permeation Effect). Otherwise, their small size allows a quick elimination by the kidney [3]. Previous phage display studies showed that TLVSSL peptide has a high affinity for phosphatidylserine, a phospholipid overexpressed on the membrane of apoptotic cells. Apoptosis is a natural process of cell death [4]. The targeting of apoptotic cells is interesting to follow the efficiency of an antitumoral therapy and for diagnosis of diseases related to this process. In this work, AGuIX nanoparticles have thus been grafted with this peptide and characterized.

Methods

The TLVSSL peptide has been grafted on nanoparticles AGuIX® by activation with EDC of carboxylic functions available on nanoparticle surface. Furthermore, previous addition of an optical dye allows their applications in optical imaging. Different techniques such as PCS, fluorescence spectroscopy, HPLC and proton relaxometry were used to characterize this platform.

Results

Relaxometric studies by NMRD profiles confirm the increase of the rotational correlation time after linking of the peptide and allow to study the time stability of the platform. The biological efficiency of this novel bimodal agent to target apoptotic cells was evaluated by fluorescence microscopy on lymphablastic human T cell line. In vitro cell apoptosis was chemically induced by incubation with campthothecin. Biological experiments has been checked by fluorescence microscopy and flow cytometry on incubated cells with labelled and grafted-AGuIX nanoparticles. RITC fluorescence intensity detection allowed to confirm the probe efficiency to target apoptosis.

Conclusion

These characterizations and biological tests confirm the binding of the peptide and the efficient targeting of apoptotic cells. Further in vivo tests will be achieved to confirm the efficiency of grafted-nanoparticles on apoptotic mouse model.

  

References

 

[1] F. Lux et Al., Angew. Chem. Int. Ed. 2011, 50, 1-6.

[2] A. Mignot et Al., Chem. Eur. J., 2013, 19, 6122-6136.

[3] G. Le Duc et Al., ACS Nano, 2011, 5, 9566-9574.

[4] C. Laumonier, thesis, 2005, Université de Mons-Hainaut, « Imagerie moléculaire : recherche de vecteurs peptidiques spécifiques de l'apoptose par la méthode du phage display ».

Keywords: Bimodal; Nanoparticles; AGuIX; Apoptosis; MRI; Optical Imaging
Comments on this paper
Andrea Wang
conclusion
Apoptotic cell characterizations are the base for the apoptotic animal models of disease characterizations.
Sherry Green
The Nanotechnology has lead a lot of change to biotech industry. It's application on sequencing may lead to another revolution on sequencing, which may be much more crazy than the Hiseq 2500, will low the price of whole genome sequencing

Susan Rey
apoptotic cells
All cells in human bodies are destined for death. this is a natural law. And it is also very important for treating all related diseases. so there are a lot of methods used to detect the cell death--apoptosis.
Mario Dentamaro
For sure, but these products are very expensive with generally an high mass protein as targeter. This new probe is a small (~5nm) bimodal contrast agent (MRI and optical imaging) based on AGuIX nanoparticles. Some research performed on these nanoparticles demonstrated that they are biocompatible and easely excreted.




 
 
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