Citric acid coated ultrasmall superparamagnetic iron oxide nanoparticles conjugated with lactoferrin for targeted negative MR imaging of glioma

Abstract

The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of −7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.

Carboxylated superparamagnetic Fe3O4 nanoparticles modified with 3-amino propanol and their application in magnetic resonance tumor imaging

“…The surface of USPIO with iron acetylacetonate as precursor is coated with polyols, which is not easy to be further modified [ 25 ]. With ferric chloride as precursor, small molecules or macromolecules containing carboxyl, amino and other compounds can be added to obtain USPIO with different surface coating, which is more widely used [ 26 ]. The thermal stability of materials is one of the indicators to select the performance of materials [ 27 ].…”

Metal-Based Nanostructured Therapeutic Strategies for Glioblastoma Treatment—An Update

“…The potential important role of SPIONs in therapy of GBM results from their ability to exhibit superparamagnetism, which allows them to accumulate at the targeted cancerous tissue when subjected to a magnetic field [ 166 ]. Therefore, SPIONs can be implemented as an effective contrast agent in MRI and may also be important diagnostic tools for the assessment of the grade of the tumor (e.g., evaluation of MRI signal intensities after the administration of probes containing neuropilin-1 and ultra-small SPIONs) [ 167 , 168 ].…”

“…It was recently reported that the properties of USPIOs could be enhanced by modification with citric acid and subsequent conjugation with lactoferrin. These improved polygonal USPIOs exhibited satisfactory distribution and biocompatibility in numerous studies, including cytotoxicity, migration and blood biochemistry analyses [ 168 ]. PEGylated USPIOs may also be conjugated with Ang-2, which promotes their passage across the BBB, allowing the nanoprobe to be delivered to GBM and improve positive contrast in MRI.…”

Ursolic acid loaded tri-block copolymer nanoparticles based on triphenylphosphine for mitochondria-targeted cancer therapy

“…The-OH of PEG can provide a polymerization reaction with the active site, and the reaction product is a block copolymer. Additionally, the hydrophilic block of PEG was introduced into the PLLA chain segment to prevent non-specific phagocytosis [23,24].…”