Synthesis of Amine Terminated Pegylated Iron Oxide Nanoparticles for Prospective Astrocytoma Resection Grade Improvement

Having a survival rate to 5 years of only 3%,Glioblastoma’s(GBM)main treatment is surgical excision.Iron oxide nanoparticles have been proved to be a magnetic resonance imaging contrast agent and,if synthesized and tuned correctly,could be used to improve complete GBM resection.In this work monodisperse iron oxide nanoparticles were synthesized using thermal decomposition method,then a ligand exchange reaction with 3-aminopropyl trimethoxysilane(APS)was performed,following Pegylation of the particles using dicarboxylic acid PEG(PEG-diacid)and finally aminating with 2,2’-(ethylenedioxy)bis(ethylamine),last two by amide reactions.STEM and DLS demonstrate monodispersity(log σ<0.2)and desired size range to penetrate the blood-brain barrier(BBB);FT-IR shows the reactions were executed correctly and finally stability in deionized water,0.07 M NaCl and PBS 1X,as a function of 0-30 days,was tested.Results revealed the importance that the oleic acid/iron oleate molar ratio and the growth stage time represents for determining iron oxide nanoparticles’ size;as well as APS concentration and nucleation time influence on silica coating when performing the ligand exchange reaction.The produced iron oxide nanoparticles exhibit stability and proper amine terminated groups which are needed to allow easy incorporation of Chlorotoxin,a 36-amino acid peptide that binds specifically to astrocytoma cells,and a fluorescent molecule,which enables real time visualization of the tumor during surgery.