Functionalization of the PEG Corona of Nanoparticles by Clip Photochemistry in Water: Application to the Grafting of RGD Ligands on PEGylated USPIO Imaging Agent

Abstract

The fast development of nanomedicines requires more and more reliable chemical tools in order to accurately design materials and control the surface properties of the nano-objects used in biomedical applications. In this study we describe a smooth and simple photografting technique, i.e., the clip photochemistry, that allows the introduction of molecules of interest in inert polymers or on stealth nanoparticles directly in aqueous solution. First we developed the methodology on polyethylene glycol (PEG) and looked for critical parameters of the process (irradiation times, concentrations, washings) by using several molecular probes and adapted analytical techniques ((19)F qNMR, EA, LSC). We found that the clip photochemistry in water is a robust and efficient method to functionalize PEG. Second we applied it on PEGylated USPIO (USPIO-PEG) magnetic resonance imaging agent and succeeded in introducing RGD peptide and homemade peptidomimetics on their PEG segments. The magnetic abilities of the conjugated nanoparticles were unchanged by the derivatization process as evidenced by their relaxometric properties and their NMRD profile. When tested on Jurkat lymphocyte T Cells, which express αvβ3 integrins, the USPIO conjugated with RGD ligands leads to an increase of the transverse relaxation rate (R2) by a factor 10 to 14 as compared to USPIO-PEG. Consequently, it makes them good candidates for targeted imaging technology in cancer therapy.

Novel Polymeric Micelles-Coated Magnetic Nanoparticles for In Vivo Bioimaging of Liver: Toxicological Profile and Contrast Enhancement

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Quantitative Fluorine NMR To Determine Carbohydrate Density on Glyconanomaterials Synthesized from Perfluorophenyl Azide-Functionalized Silica Nanoparticles by Click Reaction

“…The absolute sensitivity of 19 F is ~4700 times higher than 13 C, and only ~12% lower than 1 H. Furthermore, 19 F has negligible background interference, and the spectra are relatively simple. Quantitative 19 F NMR ( 19 F qNMR) has found important uses in quantification of fluorinated compounds in complex matrices, [36][37][38] , polymers grafted on nanoparticles, 39 and for the quan-2 titative measurement of enzymatic activity by determining released fluorinated groups from nanomaterials. [40][41][42][43][44] There has been no report on applying 19 F qNMR for the analysis of carbohydrate density on glyconanomaterials.…”

A bioanalytical assay to distinguish cellular uptake routes for liposomes

“…Efficient drug and DNA delivery carriers are highly needed in pharmacology, medicine, and biotechnology. In recent years, different systems have been developed for this purpose, e.g., lipid based nanocapsules , polymersomes , or surface‐conjugated nanoparticles . In all cases, the delivery of the cargo is a complex, multistep process: particles have to reach their targets, enter into the cells, in most cases by endocytosis, escape the endosomal membrane, and release the cargo which has to bind on the correct site .…”