Synthesis and characterization of cellulose nanocrystals/gadolinium oxide nanocomposite as a dual contrast agent for magnetic reasonance imaging

Abstract

The attractive properties of gadolinium-based nanoparticles as a positive contrast agent for magnetic resonance imaging (MRI) have piqued the interest of both researchers and clinicians. Nonetheless, due to the biotoxicity of gadolinium (III) ions' free radicals, there is a need to address this issue. Therefore, this research aimed to develop a biocompatible, dispersible, stable, hydrophilic, and less toxic cellulose nanocrystals/gadolinium oxide nanocomposite with dual-modal T1 and T2 contrast agent properties for MRI purposes. However, creating dual agents is challenging, but it can be achieved through some factors such as controlling surface coating, nanoparticle size, reducing the thickness of the coating layer, and controlling the spatial distribution of the nanoparticles. This investigation centred on utilizing the sol-gel method to synthesize Gd2O3 magnetic nanoparticles, emphasizing how temperature impacts both the crystallization process and particle size. Additionally, the acid hydrolysis technique derived cellulose nanocrystals (CNCs) from microcrystalline cellulose (MCC). A novel composite was created as a dual contrast agent to evaluate its potential for use in MRI. The cytotoxicity and cellular uptake of the nanocomposite were evaluated using MTT assay testing on HeLa cell lines. A range of chemical and physical characterizations was conducted to establish the Gd2O3-NPs produced at various temperatures (500- 1100°C). Fourier transform infrared (FTIR) spectroscopy confirmed the existence of a new band at wavenumber 448 cm−1 and 546 cm−1, which were assigned to the Gd-O stretching frequencies of the Gd2O3 cubic phase in the end-product of the Gd2O3-NPs. The additional analyses conducted on the Gd2O3 nanoparticles revealed a significant improvement in their thermal stability. The XRD results demonstrated that an annealing temperature of 1000°C was the most suitable for producing Gd2O3 nanoparticles with a high level of crystallinity and an average diameter of 65 nm. Further investigation using vibrating sample magnetometers showed that the Gd2O3 nanoparticles were paramagnetic and had a high saturated magnetization of 1.73 emu/g. The results obtained from UV-Vis spectroscopy showed that the nanoparticles had a band gap value of 4 eV and exhibited a UV-Vis absorption peak in the 245-420 nm range. The Gd2O3 nanoparticles had a spherical-like morphology and a high weight percentage. Regarding the study's second objective, the yield of CNCs demonstrated remarkable physicochemical properties. XRD analysis revealed that the crystallinity degree of the CNCs was higher than that of MCC. Moreover, the zeta potential analysis showed that the CNCs sample had highly negative surface charges. Finally, TEM analysis showed that the CNCs had a network-like structure with an average diameter of 9.36 ± 3.81nm and 83.84% crystallinity index. The FESEM analysis demonstrated a significant reduction in the size of particles and a modification in surface structure when the CNCs underwent post-acid hydrolysis. Furthermore, the biocompatibility of (CNCs- PEG/NaOH)/Gd2O3 nanocomposite synthesized at 10 kGy was assessed through MTT assay tests on HeLa cell lines, which demonstrated good biocompatibility without any cytotoxic effects for all concentrations of Gd and had sufficient cellular uptake. Moreover, displayed a remarkable enhancement effect on both T1 and T2-weighted images, with high r1 and r2 relaxivity when compared to clinical and commercial agents. Thus, this biocompatible nanocomposite has excellent potential as a dual contrast agent for MRI and other biomedical applications.