Theranostic RGD@Fe3O4-Au/Gd NPs for the targeted radiotherapy and MR imaging of breast cancer

Abstract

Background As a radiosensitizing agent in magnetic resonance imaging (MRI), gadolinium is disadvantageous in that it confers a rather high toxicity and low longitudinal comfort time (r1). We hypothesized that gadolinium when combined with gold-coated iron oxide nanoparticles (NPs), might deliver better radiosensitization in MRI-based cancer theranostics. After being synthesized ligand/receptor RGD@Fe3O4-Au/Gd nanoparticles, they were characterized via some methods, such as visible–ultraviolet spectroscopy (UV–VIS), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscope (TEM). Using relaxometry, the parameters of contrast change in T1-weighted MRI and the rate of radiation sensitivity on cancerous (MCF-7, SK-BR-3 and MDA-MB-231 (and reference (MCF-10a) breast cell lines were investigated. Results The presence of ultra-small iron oxide, gold, gadolinium, and RGD peptide as components of the RGD@Fe3O4-Au/Gd nanocomplex was confirmed by UV–visible, FTIR, EDX and XRD tests. With a size ranging from 4.124 nm (DLS) to 15 nm (TEM), these NPs exhibited a surface charge of –45.7 mV and a magnetic saturation of 3 emu/g. The concentrations of iron, gadolinium and gold samples in the nanocomplex were 1000, 1171 and 400 parts per million (ppm), respectively. In the relaxometry test, the rates of r2/r1 and r1 NPs were 1.56 and 23.5 mM−1 s−1. The dose increase factor for targeted (RGD@Fe3O4-Au/Gd) and non-targeted (Fe3O4-Au/Gd) NPs at 6 MV and 2 Gy was 89.1 and 59.1, respectively. Conclusion Owing to an enhanced signal-to-noise ratio (SNR), as confirmed by the MRI of RGD receptor-expressing MDA-MB-231 cells, RGD@Fe3O4-Au/Gd NPs were found to confer higher radiosensitization and an overall better performance as a novel radiosensitizer for MRI-based breast cancer theranostics than Fe3O4-Au/Gd nanocomplex. Graphical Abstract

Future theranostic strategies: emerging ovarian cancer biomarkers to bridge the gap between diagnosis and treatment

“…The first challenge is the targeted delivery of theranostic agents with cytotoxic payloads (conventional chemotherapeutic agents) to tumor sites (Tsourkas, 2019). The second challenge is the reliance on the enhanced-permeability-retention (EPR) effect for the accumulation of systemically administered nanoparticle-based drug delivery systems within tumor tissue, which is driven by passive diffusion and facilitated by 'leaky' tumor vasculature (Amraee et al, 2023). The third challenge is the need for active targeting, utilizing high-affinity molecules like antibodies, antibody fragments, and peptides, to achieve targeted drug and theranostic delivery to ovarian cancer cells (Slastnikova et al, 2018;Todaro et al, 2023).…”