Radiolabeled iron oxide nanoparticles functionalized with PSMA/BN ligands for dual-targeting of prostate cancer

Frontiers in Nuclear Medicine

Nuclear Medicine

Eleni K. Efthimiadou¹  Maria Theodosiou¹  Penelope Bouziotis²  Evangelia-Alexandra Salvanou²  Danae Efremia Bajwa²  Theodora S. Koutsikou³  Christos Liolios⁴ 

[1] Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece;Radiochemical Studies Laboratory, Energy & Safety, Institute of Nuclear & Radiological Sciences & Technology (INRASTES), National Centre for Scientific Research (NCSR) “Demokritos”, Athens, Greece;Radiochemical Studies Laboratory, Energy & Safety, Institute of Nuclear & Radiological Sciences & Technology (INRASTES), National Centre for Scientific Research (NCSR) “Demokritos”, Athens, Greece;Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece;Radiochemical Studies Laboratory, Energy & Safety, Institute of Nuclear & Radiological Sciences & Technology (INRASTES), National Centre for Scientific Research (NCSR) “Demokritos”, Athens, Greece;Research Laboratory, Institute of Pharmaceutical Research & Technology (IFET) (Pallini), Athens, Greece;

关键词: prostate cancer;    PSMA;    bombesin;    bispecific heterodimers;    iron oxide nanoparticles;    Tc;    SPECT;   

DOI  :  10.3389/fnume.2023.1184309

 received in 2023-03-11, accepted in 2023-08-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionProstate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer.MethodsIONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP).Results and DiscussionThe MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging.

【 授权许可】

Unknown   
© 2023 Bajwa, Salvanou, Theodosiou, Koutsikou, Efthimiadou, Bouziotis and Liolios.