Design of 99m Tc-Labeled Low Generation Dendrimer-Entrapped Gold Nanoparticles for Targeted Single Photon Emission Computed Tomography/Computed Tomography Imaging of Gliomas
Chemokine receptor-4 (CXCR4) has been demonstrated to be overexpressed in glioma cells and associated with poor survival. In the present study, we designed and synthesized 99m
Tc-labeled low-generation dendrimer-entrapped gold nanoparticles (Au DENPs), which were modified
with CXCR4-ligand for targeted single photon emission computed tomography (SPECT)/computed tomography (CT) imaging of glioma. Generation two poly(amidoamine) dendrimers were sequentially conjugated with diethylenetriamine pentacetate acid (DTPA) and polyethylene glycol (PEG) modified with
FC131 peptide (a CXCR4-specific ligand), and were then utilized as a template for entrapment of gold nanoparticles (Au NPs). After radiolabeling with 99m
Tc via DTPA chelation, the glioma-targeting SPECT/CT dual mode nanoprobe {(Au0)6-G2-99m
-DTPA-(PEG-FC131)}
DENPs were generated. The FC131-functionalized Au DENPs before and after 99m
Tc radiolabeling were well characterized. The results revealed that prior to 99m
Tc radiolabeling, FC131-functionalized Au DENPs had a uniform size distribution, acceptable biocompatibility
in the given Au concentration range and could specifically target glioma cells due to the attached FC131. Furthermore, the FC131-functionalized Au DENPs could be readily radiolabeled by 99m Tc with good radiochemical stability and high radiochemical purity. The {(Au0)6-G2-99m
Tc-DTPA-(PEG-FC131)}
DENPs appeared to be effective in targeted SPECT/CT imaging of glioma cells in vitro and in vivo in a subcutaneous tumor model. The developed FC131-functionalized dendrimer-based nanoprobe may hold a great potential for utilization in SPECT/CT imaging of different CXCR4-overexpressing
cancers.
Keywords: CXCR4; DENDRIMERS; GLIOMA; GOLD NANOPARTICLES; SPECT/CT IMAGING
Document Type: Research Article
Publication date: 01 June 2019
- Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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