Magnetic Graphene Oxide Nanocarrier as a drug delivery vehicle for MRI monitored magnetic targeting of rat brain tumors

Introduction: Glioblastoma multiform is the most common malignant brain tumor, with an invasive nature. Despite the development of conventional therapies such as surgery, radiotherapy and chemotherapy, because of high recurrence rates, the prognosis remains very poor. Over the last decade, nanotechnology has represented an innovative method as nanoparticle-based drug delivery carriers to overcome the BBB transport. Multifunctional magnetic nanoparticles are powerful tools for current clinical diagnostics, imaging and therapeutic procedures. Materials and Methods: Magnetic targeting studies were carried out in C6 glioma tumor-bearing Wistar rats using intravenous magnetic nanoparticles administration under permanent magnetic phantom. Animals were placed ventrally on a platform with their head positioned between two blocks of NdFeB permanent magnet (1.3 tesla). Measurements of magnetic density in the space between the two blocks were carried out using a tangential B-probe Teslameter (LEYBOLD, Germany). MNP (9 mg/kg) were injected into the tail vein of rats, seventeen days after implantation and retained in the magnetic field for 2h. To evaluate brain- targeting ability of nanoparticles, the rats were imaged with MRI before the administration of nanoparticles and after the magnetic targeting. Immediately following MRI, the animals were sacrificed and the brains were collected for Prussian blue staining. Results: Magnetic NGO/PLGA nanoparticles with a diameter of 71.8 nm, a zeta potential of -33.07±0.07 mV presented superior superparamagnetic properties with a saturation magnetization of 15.98 emu/g. The results of MR T2 images and Prussian blue staining of rat brains indicated MNPs could overcome the BBB for glioma targeting in the presence of a permanent magnetic field. The measured magnetic density at the GBM area was 450 mT, the value measured 2.5 cm caudal to the tumor was 325 mT, indicating that the tumor would be exposed to a maximum magnetic force. Furthermore, the MRI images demonstrated MNPs could be used in noninvasive MR imaging techniques and enhance the MRI sensitivity to offer better chemotherapy and real time monitoring. Conclusion: In the present study, for the first time, we combined the concepts from these two fields to synthesize magnetic NGO nanoparticles and indicated its high-level specificity to magnetic targeting C6 glioma rats, that its ability to serve as an excellent contrast enhancement agent for MRI.