Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units for High Relaxivity Performance in MRI

Area of Science:

• Nanotechnology
• Materials Science
• Biomedical Imaging

Background:

• Gadolinium (Gd) complexes are crucial as contrast agents in Magnetic Resonance Imaging (MRI).
• Improving the relaxivity and stability of Gd-based contrast agents is an ongoing challenge.
• Attaching Gd complexes to nanoparticles offers a strategy to enhance MRI performance and enable targeted delivery.

Purpose of the Study:

• To design and synthesize a novel octadentate gadolinium (Gd) complex with a dithiocarbamate tether.
• To immobilize this Gd complex onto gold nanoparticles (AuNPs) to create a robust MRI contrast agent.
• To evaluate the relaxivity, stability, and targeting capabilities of the resulting multifunctional nanoparticles.

Main Methods:

• Synthesis of an octadentate Gd-DO3A complex functionalized with a dithiocarbamate group.
• Attachment of the Gd complex to the surface of ~4.4 nm gold nanoparticles via the dithiocarbamate tether.
• Characterization of the immobilized complex and measurement of relaxivity (r1) at different magnetic field strengths and temperatures.
• Functionalization of the nanoparticle surface with polyethylene glycol (PEG), thioglucose, and folic acid for biocompatibility and targeting.

Main Results:

• Successful design and robust attachment of the Gd complex to AuNPs.
• Significant increase in relaxivity (r1) upon immobilization: from 4.0 mm⁻¹s⁻¹ (unbound) to 34.3 mm⁻¹s⁻¹ (at 10 MHz) and 22±2 mm⁻¹s⁻¹ (at 63.87 MHz).
• The one-pot synthesis allowed for versatile preparation of multifunctional nanoparticles.
• Surface functionalization with PEG, thioglucose, and folic acid minimally impacted relaxivity and introduced targeting capabilities.
• The nanoparticles demonstrated potential for passive and active targeting (via folate receptors) of cancer cells like HeLa.

Conclusions:

• Immobilization of the octadentate Gd complex on gold nanoparticles dramatically enhances relaxivity.
• The developed multifunctional nanoparticles are non-toxic, robust, and suitable for advanced MRI applications.
• The incorporation of targeting ligands like folic acid opens avenues for targeted cancer imaging and therapy.