Azide‐PEG‐Folate Functionalized Gadolinium Nanoparticles: A Preliminary Click‐Chemistry Platform for Magnetic Resonance Imaging Contrast

Gadolinium nanoparticles (GdNPs) have been studied extensively due to their lower toxicity and better magnetic resonance imaging (MRI) detection capabilities than Gd‐chelates. Their surfaces are conveniently modified with several molecules to enhance their accumulation in the cancer of interest, thereby enabling more accurate diagnosis and treatment. In this study, hydrothermal GdNPs were functionalized with folic acid (FA) (for active targeting), polyethylene glycol (to improve biocompatibility), and azide molecules (for subsequent click reaction) via a silane ligand exchange conjugation method. Results showed a hydrodynamic diameter of 7.90 nm and a zeta potential of −6.80 mV for Azide‐PEG‐Folate‐modified GdNPs. UV spectra confirmed the presence of FA in NPs at UV absorption of 284 and 353 nm. Typical FTIR spectra also appeared at wavenumbers of 2950 and 2150 cm ^{− 1} , confirming the presence of PEG and azide molecules on modified NPs, respectively. Additionally, modified NPs maintained good stability for up to 3 weeks at 25 and 4 °C. A preliminary click in vitro investigation also showed the NPs’ good viability even after incubation at 132 µg/mL, followed by the click reaction with 300 µg/mL of Holmium(III)‐complexed‐DOTA‐BCN on HeLa cancer cells. This first click‐combination finding serves as a promising candidate for Gd/Ho‐MRI agents, thereby enabling a more accurate diagnosis due to their simultaneous T ₁ /T ₂ contrast enhancement.