Synthesis of specific nanoparticles for targeting tumor angiogenesis using electron-beam irradiation

Abstract

International audienceAngiogenesis plays a critical role in both growth and metastasis of tumors. Vascular endothelial growth factor (VEGF) is an endogenous mediator of tumor angiogenesis. Blocking associations of the VEGF with its corresponding receptors (KDR) have become critical for anti-tumor therapy. Acyclo-peptide (CBO- P11), derived from VEGF, able to inhibit the interaction between the growth factor and its receptor, was synthesized in our laboratory to provide a target for angiogenesis. We have prepared biocompatible poly(vinylidenefluoride (PVDF) nanoparticles in order to obtain long blood circulating systems. Electron-beam (EB) irradiation was used to activate the PVDF nanoparticles. From electron paramagnetic resonance (EPR) measurements, we studied the radical stability in order to optimize the radio-grafting of acrylicacid (AA). Further functionalization of PVDF-g-PAA nanoparticles with the cyclo-peptide via a spacer arm was also possible by performing coupling reactions. High resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) and MALDI mass spectrometry allowed us to follow each chemical step of this peptide immobilization. We designed a new nanodevice suggesting a great potential for targeting angiogenesis

“Click” Conjugation of Peptide on the Surface of Polymeric Nanoparticles for Targeting Tumor Angiogenesis

“…Radiation initiation is one of the cleanest grafting methods available, since molecular initiator or catalysts are not required. In a previous work, we reported the grafting of AA on PVDF nanoparticles after their irradiation (postradio-grafting) (19). However, electron paramagnetic resonance and differential scanning calorimetry studies showed a relative instability of radicals initiated under irradiation in comparison with PVDF films, decreasing the radical amount available for post-polymerization of AA.…”

“…PVDF nanoparticles were prepared by emulsion polymerization of corresponding monomer (VF2) as previously described (19). Two different syntheses were run in the presence or in the absence of surfactant.…”

“…Radical polymerization in aqueous emulsion was used to produce PVDF nanoparticles according to a previously described procedure (19). In order to assess the influence of surfactant on the size of these particles, two different batches of PVDF nanoparticles were prepared in the presence or in the absence of perfluorooctanoic acid (POA).…”

“…PVDF is a hydorphobic polymer, suggesting that it could be coated with a hydrophilic layer to get a core/shell structure and then can be used as drug delivery system. According to an optimized process from a preliminary study (19), nanoparticles were consequently coated with poly(acrylic acid) (PAA), using electron-beam irradiation yielding PVDF-g-PAA nanoparticles.…”

HR-MAS NMR Spectroscopy in Material Science

“…Through a careful analysis of these iron oxide systems, the surface structure and ligand binding (chelation) configuration was determined, and in several cases were quite different from the standard single point attachment proposed by others. [58] 1 H HR-MAS NMR has also been used to look at the surface modification in polymer based NPs, including the monitoring of multiple synthetic steps employed during the peptidesurface modification of poly(vinylidene fluoride) (PVDF) nanoparticles, [60] or the surface modification of Dendron based NPs. [61] Polystyrene embedded silver clusters produced by a thermolysis reactions have also been characterized using HR-MAS NMR.…”