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Published on: May 2, 2016
Preclinical Evaluation of NHS-Activated Gold Nanoparticles Functionalized with Bombesin or Neurotensin-Like Peptides
Livia Elena Chilug1,2, Dana Niculae1, Radu Anton Leonte1
1Radiopharmaceutical Research Centre, Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering, 30 Reactorului Street, Magurele, 077125 Ilfov, Romania.
Abstract:
Recent advances and large-scale use of hybrid imaging modalities like PET-CT have led to the necessity of improving nano-drug carriers that can facilitate both functional and metabolic screening in nuclear medicine applications. In this study, we focused on the evaluation of four potential imaging nanoparticle structures labelled with the 68Ga positron emitter. For this purpose, we functionalized NHS-activated PEG-gold nanoparticles with 68Ga-DOTA-Neuromedin B, 68Ga-DOTA-PEG(4)-BBN(7-14), 68Ga-DOTA-NT and 68Ga-DOTA-Neuromedin N. In vitro binding kinetics and specific binding to human HT-29 colon carcinoma cells and DU-145 prostate carcinoma cells respectively were assessed, over 75% retention being obtained in the case of 68Ga-DOTA-PEG(4)-BBN(7-14)-AuNP in prostate tumour cells and over 50% in colon carcinoma cells. Biodistribution in NU/J mice highlighted a three-fold uptake increase in tumours at 30 min post-injection of 68Ga-DOTA-NT-AuNP and 68Ga-DOTA-PEG(4)-BBN(7-14)-AuNP compared to 68Ga-DOTA-NT and 68Ga-DOTA-PEG(4)-BBN(7-14) respectively, therewith fast distribution in prostate and colon tumours and minimum accumulation in non-targeted tissues.
Insights
Researchers developed novel Gallium-68 (68Ga) labeled gold nanoparticles for enhanced cancer imaging. These nanoparticles show promising uptake in colon and prostate tumor cells, improving diagnostic capabilities in nuclear medicine.
Area of Science:
- Nuclear Medicine
- Nanotechnology
- Oncology
Background:
- Hybrid imaging modalities like PET-CT require advanced nano-drug carriers for functional and metabolic screening.
- Improving nanoparticle-based drug carriers is crucial for enhanced nuclear medicine applications.
Purpose of the Study:
- To evaluate four Gallium-68 (68Ga) labeled nanoparticle structures as potential imaging agents.
- To assess the in vitro binding kinetics and specificity of these nanoparticles to cancer cells.
- To determine the in vivo biodistribution and tumor uptake of the nanoparticles.
Main Methods:
- Functionalization of PEG-gold nanoparticles with 68Ga-DOTA conjugates: 68Ga-DOTA-Neuromedin B, 68Ga-DOTA-PEG(4)-BBN(7-14), 68Ga-DOTA-NT, and 68Ga-DOTA-Neuromedin N.
- In vitro assessment of binding kinetics and specific binding to HT-29 colon and DU-145 prostate carcinoma cells.
- In vivo biodistribution studies in NU/J mice to evaluate tumor uptake and off-target accumulation.
Main Results:
- 68Ga-DOTA-PEG(4)-BBN(7-14)-AuNP demonstrated over 75% retention in prostate cancer cells and over 50% in colon cancer cells.
- Biodistribution studies showed a three-fold increase in tumor uptake at 30 min post-injection for 68Ga-DOTA-NT-AuNP and 68Ga-DOTA-PEG(4)-BBN(7-14)-AuNP compared to their non-nanoparticle counterparts.
- Nanoparticles exhibited rapid distribution in prostate and colon tumors with minimal accumulation in non-targeted tissues.
Conclusions:
- The evaluated 68Ga-labeled gold nanoparticles show potential as effective imaging agents for prostate and colon cancers.
- Nanoparticle formulation significantly enhances tumor targeting and retention compared to non-conjugated tracers.
- These findings support the development of advanced nano-drug carriers for improved nuclear medicine diagnostics.
