Aminosilanized flower-structured superparamagnetic iron oxide nanoparticles coupled to 131I-labeled CC49 antibody for combined radionuclide and hyperthermia therapy of cancer

Int J Pharm. 2020 Sep 25:587:119628. doi: 10.1016/j.ijpharm.2020.119628. Epub 2020 Jul 15.

Abstract

Combined radionuclide therapy with magnetic nanoparticles-mediated hyperthermia has been under research focus as a promising tumor therapy approach. The objective of this study was to investigate the potential of 131I-radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) prepared as the ~40 nm flower-shaped structures with excellent heating efficiency (specific absorption rate at H0 = 15.9 kA∙m-1 and resonant frequency of 252 kHz was 123.1 W∙g-1) for nano-brachytherapy of tumors. 131I-radiolabeled CC49 antibody attached to SPIONs via reactive groups of 3-aminopropyltriethoxysilane (APTES) provided specificity and long-lasting localized retention after their intratumoral application into LS174T human colon adenocarcinoma xenografts in NOD-SCID mice. The results demonstrate feasibility and effectiveness of magnetic hyperthermia (HT), radionuclide therapy (RT) and their combination (HT + RT) in treating cancer in xenograft models. Combined therapy approach induced a significant (p < 0.01) tumor growth suppression in comparison to untreated groups presented by the tumor volume inhibitory rate (TVIR): 54.38%, 68.77%, 73.00% for HT, RT and HT + RT, respectively in comparison to untreated group and 48.31%, 64,62% and 69,41%, respectively, for the SPIONs-only injected group. Histopathology analysis proved the necrosis and apoptosis in treated tumors without general toxicity. Obtained data support the idea that nano-brachytherapy combined with hyperthermia is a promising approach for effective cancer treatment.

Keywords: CC49 monoclonal antibody; Combined therapy; Hyperthermia; Nano-brachytherapy; Nano-radiopharmaceuticals; Radionuclide ((131)I) therapy; Superparamagnetic nanoparticles.

MeSH terms

  • Animals
  • Antibodies, Neoplasm
  • Hyperthermia
  • Hyperthermia, Induced*
  • Iodine Radioisotopes
  • Magnetic Iron Oxide Nanoparticles
  • Magnetite Nanoparticles*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasms* / therapy

Substances

  • Antibodies, Neoplasm
  • B72.3 antibody
  • Iodine Radioisotopes
  • Iodine-131
  • Magnetite Nanoparticles