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

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 ~40nm flower-shaped structures with excellent heating efficiency (specific absorption rate at H0=15.9 kA∙m-1 and resonant frequency of 252kHz was 123.1W∙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.