» Articles » PMID: 39380961

Radiolabeled Iron Oxide Nanoparticles Functionalized with PSMA/BN Ligands for Dual-targeting of Prostate Cancer

Overview
Journal Front Nucl Med
Date 2024 Oct 9
PMID 39380961
Authors
Affiliations
Soon will be listed here.
Abstract

Introduction: Prostate 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.

Methods: IONs 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 (Tc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP).

Results And Discussion: The 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 Tc-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.

References
1.
Malhotra N, Lee J, Liman R, Ruallo J, Villaflores O, Ger T . Potential Toxicity of Iron Oxide Magnetic Nanoparticles: A Review. Molecules. 2020; 25(14). PMC: 7397295. DOI: 10.3390/molecules25143159. View

2.
Eder M, Schafer M, Bauder-Wust U, Hull W, Wangler C, Mier W . 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012; 23(4):688-97. DOI: 10.1021/bc200279b. View

3.
Guo P, Huang J, Moses M . Cancer Nanomedicines in an Evolving Oncology Landscape. Trends Pharmacol Sci. 2020; 41(10):730-742. DOI: 10.1016/j.tips.2020.08.001. View

4.
Chakravarty R, Goel S, Dash A, Cai W . Radiolabeled inorganic nanoparticles for positron emission tomography imaging of cancer: an overview. Q J Nucl Med Mol Imaging. 2017; 61(2):181-204. PMC: 5477426. DOI: 10.23736/S1824-4785.17.02969-7. View

5.
Maurer T, Eiber M, Schwaiger M, Gschwend J . Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016; 13(4):226-35. DOI: 10.1038/nrurol.2016.26. View