Preclinical Evaluation of NHS-Activated Gold Nanoparticles Functionalized with Bombesin or Neurotensin-Like Peptides for Targeting Colon and Prostate Tumours

Molecules. 2020 Jul 24;25(15):3363. doi: 10.3390/molecules25153363.

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.

Keywords: 68Ga; PET imaging; bombesin; colon cancer; drug delivery; gold nanoparticles; neurotensin; prostate cancer.

MeSH terms

  • Animals
  • Biological Availability
  • Bombesin / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / diagnostic imaging*
  • Colonic Neoplasms / metabolism
  • Gallium Radioisotopes / administration & dosage
  • Gallium Radioisotopes / chemistry
  • Gallium Radioisotopes / pharmacokinetics
  • Gold / administration & dosage*
  • Gold / chemistry
  • Gold / pharmacokinetics
  • HT29 Cells
  • Humans
  • Male
  • Metal Nanoparticles / chemistry
  • Mice
  • Neoplasm Transplantation
  • Neurokinin B / analogs & derivatives*
  • Neurokinin B / chemistry
  • Neurotensin / chemistry*
  • Peptide Fragments / chemistry*
  • Peptides / administration & dosage
  • Peptides / chemistry*
  • Peptides / pharmacokinetics
  • Positron-Emission Tomography
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism
  • Receptors, Bombesin / metabolism
  • Receptors, Neurotensin / metabolism

Substances

  • Gallium Radioisotopes
  • Peptide Fragments
  • Peptides
  • Receptors, Bombesin
  • Receptors, Neurotensin
  • neuromedin N
  • Neurotensin
  • Gold
  • Neurokinin B
  • neuromedin B
  • Bombesin