AUTHOR=Lepareur Nicolas , Leal E Costa Loleh , Bocqué Maëva , Blondelle Clément , Ruello Clément , Desjulets Marie , Noiret Nicolas , Cammas-Marion Sandrine 

TITLE=Development of Biocompatible and Functional Polymeric Nanoparticles for Site-Specific Delivery of Radionuclides

JOURNAL=Frontiers in Medicine

VOLUME=2

YEAR=2015

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2015.00063

DOI=10.3389/fmed.2015.00063

ISSN=2296-858X

ABSTRACT=<sec id="ST1"><title>Introduction</title><p>Encapsulation of biologically active molecules into nanoparticles (NPs), for site-specific delivery, is a fast growing area. These NPs must be biocompatible, non-toxic, and able to release their load in a controlled way. We have developed a series of NPs based on (bio)degradable and biocompatible poly(malic acid) derivatives, poly(benzyl malate) (PMLABe), with its PEG-grafted stealth analog and target-specific biotin-PEG-<italic>b</italic>-PMLABe one. A lipophilic radiotracer has then been encapsulated into these NPs.</p></sec><sec id="ST2"><title>Methods</title><p>Monomers were synthesized from <sc>dl</sc>-aspartic acid. PEG<sub>42</sub>-<italic>b</italic>-PMLABe<sub>73</sub> and Biot-PEG<sub>66</sub>-<italic>b</italic>-PMLABe<sub>73</sub> block copolymers were obtained by anionic ring-opening polymerization of benzyl malolactonate in presence of α-methoxy-ω-carboxy-PEG<sub>42</sub> and α-biotin-ω-carboxy-PEG<sub>66</sub> as initiators. NPs were prepared by nanoprecipitation. Size, polydispersity, and zeta potential were measured by dynamic light scattering (DLS) and zetametry. <sup>99m</sup>Tc-SSS was prepared as previously described. Encapsulation efficacy was assessed by varying different parameters, such as encapsulation with preformed NPs or during their formation, influence of the solvent, and of the method to prepare the NPs. After decay, <sup>99m</sup>Tc-loaded NPs were also analyzed by DLS and zetametry. NPs’ morphology was assessed by transmission electron microscopy.</p></sec><sec id="ST3"><title>Results</title><p><sup>99m</sup>Tc-SSS was added during nanoprecipitation, using two different methods, to ensure good encapsulation. Radiolabeled NPs present increased diameters, with identical low polydispersity indexes and negative zeta potentials in comparison to non-radiolabeled NPs.</p></sec><sec id="ST4"><title>Conclusion</title><p>A radiotracer was successfully encapsulated, but some further optimization is still needed. The next step will be to modify these radiolabeled NPs with a hepatotrope peptide, and to replace <sup>99m</sup>Tc with <sup>188</sup>Re for therapy. Our team is also working on drugs’ encapsulation and grafting of a fluorescent probe. Combining these modalities is of interest for combined chemo-/radiotherapy, bimodal imaging, and/or theranostic approach.</p></sec>