Magnetic-nanoparticles as a theranostic tool for liver metastases in a murine model

Introduction: The treatment of liver metastases is still a challenge. Magnetic hyperthermia is being explored as a new therapy. Functionalized magnetic nanoparticles (MNP) can be adhered to tumour tissues and then heated... [ view full abstract ]

Introduction: The treatment of liver metastases is still a challenge. Magnetic hyperthermia is being explored as a new therapy. Functionalized magnetic nanoparticles (MNP) can be adhered to tumour tissues and then heated selectively by an alternating magnetic field (AMF). The temperature increment due to the MNP heating of MNP might destroy the tumours spearing healthy liver tissue. The aim of our experiment was to develop a reliable and selective magnetic-hyperthermia therapy for diagnosis and treatment of liver metastases in a rat model. RGD-peptides functionalized MNP, intravascular infusion of MNP and an electromagnetic applicator to achieve selective heating have been designed and an “in vivo” experiment was carried out to check the effectivity of the treatment.
Methods: Colorectal cancer cells were inoculated into the left lateral liver lobe (LLL) of WAG/RijHsd rats. Fe3O4 nanoparticles covered with PMAO and functionalized with RGD peptides were synthetized in order to adhere them to the tumour tissue. Using a microcannula placed into the hepatic artery, MNP-group was infused with MNP and saline-group was infused with the same volume of saline. After 12 hours, MRI studies were practised by 1,5T MRI machine and magnetic hyperthermia was applied by an alternating magnetic field of 14kA/m intensity and 606kHz frequency, during 21 minutes. The temperature was monitored with 3 probes placed in the tumour, LLL and rectum. 12 hours later, both groups were sacrificed and the liver removed for histopathological analysis.
Results: MRI study showed decay of the signal intensity (SI) in the liver and in the periphery of the tumour. Moreover, scattered foci may be observed within the tumours. After thermal exposure, tumour temperature increased 4.66 ± 0.99ºC in saline-group and 7.89 ± 1.2ºC in MNP group (p<0.001) (Figure 1). The values of the necrotic tissue, relative to the total tumour tissue, ranged between 1-13% and 13-99% for the saline-group and MNP-group (p<0.01), respectively.
Discussion: MNP adhered to liver metastases and could be monitored by MRI. A higher thermal increase in liver and tumour tissue was reached in MNP-infused animals, showing that MNP can be used in magnetic hyperthermia therapy, although further experiments are needed.