Physical and Biological Properties of 5-Fluorouracil Polymer-Coated Magnetite Nanographene Oxide as a New Thermosensitizer for Alternative Magnetic Hyperthermia and a Magnetic Resonance Imaging Contrast Agent: In Vitro and In Vivo Study

Abstract

This study reports a new procedure for utilizing 5fluorouracil (5-Fu)-loaded polycaprolactone (PCL)/chitosan-covered magnetite nanographene oxide (5-Fu/SPION/NGO@PCL−LMWC) as a platform for synergistic thermo−chemotherapy. In fact, superparamagnetic iron oxide nanoparticles/nanographene oxide (SPION/ NGO) nanoparticles can be coated with copolymers PCL/chitosan to attain better colloidal stability in the biological environment. Nanoparticles were synthesized and characterized for their size, surface charge, X-ray patterns, polymer content, and in vitro heat-triggered release. In vitro cytotoxic effects of nanoparticles on CT-26 cells were assessed with an MTT assay and real-time polymerase chain reaction. In vivo tumor growth inhibition was evaluated on an allograft mouse model of CT-26 cells. Tumor-bearing mice were injected with 5-Fuloaded nanoparticles intravenously, and then, the targeted delivery was amplified using a magnetic field and finally exposed to an alternating magnetic field (AMF) (40 A/m, 13.56 MHz), during which the tumor site temperature increased to 43 °C. By using an infrared camera, we managed to heat the nanoparticles up to a constant temperature between 42.5 and 43.5 °C, with a tolerance ±0.03 °C. Finally, in vitro results showed that 5-Fu-loaded nanoparticles combined with AMF hyperthermia significantly reduced the plating efficiency of the cells (P < 0.01) and increased the Bax/Bcl-2 ratio (1.42 times, P < 0.01) compared with those achieved with each one alone. Furthermore, in vivo results demonstrated that the treatment of 5-Fu-loaded nanoparticles combined with the AMF diminished the growth of CT-26 tumor cells and increased the life span of the tumor-bearing mice (P < 0.001) by thermal energy deposition compared to that of the free 5-Fu drug. Also, the high level of accumulation of the nanoparticles within the tumor site was easily monitored with magnetic resonance imaging. It was concluded that the multifunctional magnetic nanoparticles could be used as a promising nanocarrier platform for achieving concurrent goals, drug delivery, magnetic targeting, thermal-sensitizing, cell death induction, and real-time monitoring of response to treatment.

Emerging importance of nanotechnology-based approaches to control the COVID-19 pandemic; focus on nanomedicine iterance in diagnosis and treatment of COVID-19 patients

“…Otechnology in medicine finds importance in several overlapping molecular technologies [ 133 , [135] , [136] , [137] , [138] ].…”

Nanoscale Contrast Agents for Magnetic Resonance Imaging: A Review

“…The designed 5-fluorouracil-loaded polycaprolactone/chitosan-covered magnetite nano-GO materials with high accumulation within the tumor sites were deployed as MRI NCAs. These NPs with biocompatibility and high-sensitivity advantages could be applied for drug delivery and thermal-sensitizing, cell death induction as well as MRI-based diagnostic purposes . Superparamagnetic cobalt ferrite/GO nanocomposites were developed via a sonochemical technique for MRI and controlled drug delivery for simultaneous cancer diagnosis and chemotherapy .…”

Magnetic nanocarriers adorned on graphene: promising contrast-enhancing agents with state-of-the-art performance in magnetic resonance imaging (MRI) and theranostics

“…113 Hyperthermia, also known as green therapy, is extensively used as an adjuvant therapy with chemo and/or radiotherapy, leading to a significant improvement in the outcomes for cancer therapy. Recently, Kiamohammadi and co-workers proposed a novel strategy for exploiting the 5-Fu/SPION/ NGO@PCL-LMWC as an MRI contrast agent and as a new platform for synergistic thermo-chemotherapy; 114 5-Fu-loaded nanoparticles were injected into tumor-bearing mice. The targeted delivery was subsequently amplified using a magnetic field before being exposed to an alternating magnetic field (AMF).…”