Slowdown intracranial glioma progression by optical hyperthermia therapy: study on a CT-2A mouse astrocytoma model

Metallic nanorods are promising agents for a wide range of biomedical applications. We report an optical hyperthermia method capable of inducing slowdown tumor progression of an experimental in vivo CT-2A glioblastoma tumor. The tumor model used in this research is based on the transplantation of mouse astrocytoma CT-2A cells in the striatum of mice by intracranial stereotaxic surgery. Two weeks after cell implant, the resulting tumor is treated by irradiating intratumoral injected gold nanorods, biofunctionalized with CD133 antibody (B-GNRs), using a continuous wave laser. Nanoparticles convert the absorbed light into localized heat (reaching up to 44 °C) due to the effect of surface plasmon resonance. A significant slowdown in CT-2A tumor progression is evident, by histology and magnetic resonance imaging, at one (p = 0.03) and two weeks (p = 0.008) after irradiation treatment. A notable deceleration in tumor size (15%-75%) as compared to the control untreated groups, it is observed. Thus, laser irradiation of B-GNRs is found to be effective for the treatment of CT-2A tumor progression. Similarities between the pre-clinical CT-2A tumor model and the human astrocytoma disease, in terms of anatomy, metastatic behavior and histopathology, suggest that hyperthermic treatment by laser irradiation of B-GNRs administered into high-grade human astrocytoma might constitute a promising alternative treatment to limit the progression of this deadly disease.
We thank Ms Soledad Martinez (cell culture experiments), Centre for Biomedical Technology (CTB) for technical help. Also, PhD Teresa López de Mora for critical reading of the manuscript. The authors are thankful to their grant supporters, Universidad Nacional Experimental del Táchira (UNET)— Venezuela to Oscar Casanova-Carvajal. This study was also financially supported in part by CIBER-BBN (Spain) and NEUROCENTRO-CM (B2017/BMD-3760) consortium. Characterization of the MNPs has been performed by the ICTS 'NANBIOSIS', Unit 15 (Functional Characterization of Magnetic Nanoparticles) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the Center for Biomedical Technology (CTB) of the 'Universidad Politécnica de Madrid' (UPM). This work was carried out as part of Project PGC2018-097531-B-I00, funded by the Ministry of Science of Spain.