Design and Evaluation of Radiolabeled Drug Delivery System as a Multimodal Imaging Agent
Project no. 22867 · Status: Kapanmış (Yayın bekleniyor) · 2021
Summary
<p>In this study, it is aimed to synthesize multimodal nanoparticle system doxorubicin (DOX)-loaded polymeric iron oxide nanoparticles to radiolabel with zirconium-89 (89Zr) and investigate the biological behaviour of this structure in vitro and in vivo. The structural properties of the multimodal polymeric iron oxide nanoparticle system (PPLN-IO) prepared by the emulsion solvent evaporation method were characterized by Zeta Potential Analysis, Dynamic Light Scattering (DLS) method, Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) images. Nanoparticles were conjugated with biotin molecule for receptor targeting. For radiolabeling studies, the chelating agent deferoxamine-p-SCN (DFO) was conjugated to DOX-loaded PPLN-IO-BIO nanoparticles (PPLN-IO-BIO-DFO). Radiolabeling of DOX-loaded PPLN-IO-BIO-DFO nanoparticles with 89Zr at 37 oC accomplished with 78.16 ± 10.24% efficiency. The drug entrapment capacity of DOX-loaded PPLN-IO nanoparticles was determined by high-performance liquid chromatography (HPLC). In order to determine the biological behaviours of DOX-loaded PPLN-IO-BIO nanoparticles in vitro, cytotoxicity studies were performed on biotin-positive A549 lung epithelial (adenocarcinoma) and biotin-negative HEK-293 kidney epithelial (normal) cells. When the 48th hour data were examined, the IC50 value was 175.19 ± 10.56 µg/mL in HEK-293 cell line, this value was 12.43 ± 5.82 µg/mL in A549 cell line. As a result of in vitro cytotoxicity studies, it was determined that DOX-loaded PPLN-IO-BIO nanoparticles showed more toxic effects on the A549 cell line, which has a biotin receptor. A biodistribution study was performed on healthy female nude mice to determine the in vivo behaviour of DOX-loaded PPLN-IO-BIO-DFO nanoparticles. As a result of the biodistribution study, uptake was detected in the liver and lung. It is concluded that the system developed DOX-loaded PPLN-IO-BIO-DFO multimodal nanoparticle could make contribution to improve an easy prepared, target specific and biocompatible diagnostic agent.</p><p>Keywords: Doxorubicin, multimodal nanoparticles, biotin, zirconium-89, in vitro/in vivo</p>