90Y-CA/SPIONs for dual magnetic hyperthermia-radionuclide nanobrachytherapy of solid tumours

Abstract

Radiolabelled superparamagnetic iron oxide nanoparticles (SPIONs) are a promising nanomaterial for the development of dual radiation/hyperthermia cancer therapy. To that purpose, flower-shaped SPIONs with an exceptional heating capability were synthesised and coated with citrate, dextran or (3-aminopropyl)triethoxysilane. Both non-coated and coated SPIONs were nontoxic to CT-26 mouse colon cancer cells up to 1.0 mg ml−1 in vitro. In an oscillating magnetic field, citrate-coated SPIONs (CA/SPIONs) displayed the highest heating rate (SAR ∼ 253 W g−1) and the strongest hyperthermia effects against CT-26 cells. Labelling of the CA/SPIONs by the 90Y radionuclide, emitting β− radiation with an average/maximum energy of 0.94/2.23 MeV, and deep tissue penetration generated 90Y-CA/SPIONs intended for the therapy of solid tumours. However, intravenous injection of 90Y-CA/SPIONs in CT-26 xenograft-bearing mice resulted in low tumour accumulation. On the contrary, intratumoural injection resulted in long-term retention at the injection site. A single intratumoural injection of 0.25 mg CA/SPIONs followed by 30-min courses of magnetic hyperthermia for four consecutive days caused a moderate antitumour effect against CT-26 and 4T1 mouse tumour xenografts. Intratumoural application of 1.85 MBq/0.25 mg 90Y-CA/SPIONs, alone or combined with hyperthermia, caused a significant (P ≤ 0.01) antitumour effect without signs of systemic toxicity. The results confirm the suitability of 90Y-CA/SPIONs for monotherapy or dual magnetic hyperthermia-radionuclide nanobrachytherapy (NBT) of solid tumours.