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Diamond nanoparticles - antiangiogenic factor in brain cancer therapy?

Marta Grodzik ,  Ewa Sawosz Chwalibóg ,  Mateusz Wierzbicki ,  Sławomir Jaworski ,  Marta Prasek 

Warsaw University of Life Sciences, Nowoursynowska 159C, Warsaw 02-787, Poland

Abstract

Gliomas are the most common primary brain tumors, glioblastoma multiforme (GBM) being the most aggressive subtype. One of the most effective forms of antiglioma therapy is antiangiogenic therapy. Inhibition of tumor angiogenesis suppresses both tumor growth and metastasis. A large number of pro- and anti-angiogenic cellular factors regulate angiogenesis in glioblastoma. Among them, vascular endothelial growth factor (VEGF) has been implicated as a major mediator in the pathogenesis of glioblastoma. The increased protein level of VEGF is linked to the higher permeability of the blood vessels and their untypical structure, which is characteristic for tumors. Lowering of the VEGF level contributes to the normalization of blood vessels, facilitating the infiltration of other factors into the tumor, while inhibiting VEGF expression limits the transport of nutrients and oxygen into cancer cells. Recently, the new biologically active substances have appeared that can be useful in antiangiogenic therapy: nanoparticles of carbon allotropes [1] (C60 fullerenes, graphite nanoparticles, multi-walled carbon nanotubes, single-walled carbon nanotubes and diamond nanoparticles). Moreover, carbon nanoparticles are bioactive and biocompatible [2].  

We evaluated interaction between diamond nanoparticles and angiogenesis in inducted tumor. The study was conducted on multiforme glioblastoma cells (U87MG) cultured on the chicken embryo chorio-allantoic membrane (CAM). The analysis were made on stereoscope microscope, transmission electron microscope (TEM) and scanning electron microscope (SEM). Moreover the expression of proangiogenic genes: FGF-2 (basic fibroblast growth factors), VEGF (vascular endothelial growth factor) and VEGFR (vascular endothelial growth factor receptor) was evaluated. Determination of vascular permeability was performed with using dextran-FITC  particles (70 000 kDa).

Nanoparticles of diamond significantly decreased tumor mass and volume, and vessels’ area. We also found effect on blood vessels structure. Under the influence of diamond nanoparticles was observed the decrease blood vessels permeability and different structure of blood capillaries in glioblastoma tumors. qPCR analysis showed down regulated gene expression of VEGF and FGF-2 on mRNA level [3].

The present results demonstrate antiangiogenic activity of carbon nanoparticles, making them the potential factors for anticancer therapy.

 [1] Murugesan S et al (2003) FEBS Lett 6: 1157–1160 

[2] Holt KB (2007) Phil Trans R Soc A 365: 2845–2861

[3]Grodzik M et al (2011) Int J Nanomedicine 6: 3041-3048

 

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Presentation: Poster at Nano-Biotechnologia PL, by Marta Grodzik
See On-line Journal of Nano-Biotechnologia PL

Submitted: 2012-06-26 04:46
Revised:   2012-06-26 04:46