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Detection of dopamine receptors using nanoscale dendrimer for potential application in targeted delivery and whole-body imaging: synthesis and in vivo organ distribution
Ramezani Farani, M ; Sharif University of Technology | 2022
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- Type of Document: Article
- DOI: 10.1021/acsabm.2c00118
- Publisher: American Chemical Society , 2022
- Abstract:
- Dopamine is one of the most important neurotransmitters released by neurons in the central nervous system, and a variety of neurological illnesses and mental disorders are associated with impairments in the secretion and functionality of dopamine. Dopamine, depending on the type of receptors, can act as a stimulant or an inhibitor. In this study, dendrimer-conjugated dopamine was utilized as a chelating agent for Technetium-99m to investigate the organ distribution of this compound in vivo using the single-photon emission computed tomography (SPECT) technique. For this purpose, dendrimers were synthesized using polyethylene glycol diacid and citric acid precursors, and dopamine was conjugated to the dendrimer using EDC/NHS cross-linker. The results showed no sign of toxicity of the dopamine-functionalized dendrimers on HEK-293 cell lines. The optimization of labeling conditions was conducted using the experimental design method (i.e., conjugate value, pH, and the amount of reducing agent), and then labeling efficiency was evaluated by thin-layer chromatography (TLC). Finally, the study of organ distribution in normal mice using SPECT imaging and comparing it with gene expression in different organs revealed that dopamine D1 receptors exhibited the highest accumulation in the liver and that the drug retained its specificity. © 2022 American Chemical Society. All rights reserved
- Keywords:
- Central nervous system ; Dendrimer ; Dopamine ; Polyethylene glycol ; SPECT imaging ; Technetium-99m ; Amines ; Cell culture ; Chelation ; Dendrimers ; Gene expression ; Mammals ; Neurophysiology ; Particle beams ; Polyethylene glycols ; Polyethylenes ; Thin layer chromatography ; Central nervous systems ; In-vivo ; Nano scale ; Organ distribution ; Single-photon emission computed tomography imaging ; Targeted delivery ; Tomography imaging ; Whole-body imaging ; Single photon emission computed tomography ; Dopamine receptor ; Animal ; Chemistry ; HEK293 cell line ; Human ; Mouse ; Animals ; Dopamine ; HEK293 Cells ; Humans ; Mice ; Receptors, Dopamine ; Technetium
- Source: ACS Applied Bio Materials ; Volume 5, Issue 4 , 2022 , Pages 1744-1755 ; 25766422 (ISSN)
- URL: https://pubs.acs.org/doi/10.1021/acsabm.2c00118