Effect of Size, Charge, and Surface Functionalization of Gadolinium Nanoparticles on Biocompatibility and Cellular Uptake as Magnetic Resonance Imaging Contrast Agents

Gadolinium nanoparticles (GdNPs) are nanomaterials with great potential to be applied as MRI contrast agents. GdNPs have been widely explored in recent years as a T1 contrast agent with high performance due to the large relaxivity value (r1) compared to commercial Gd-based contrast agents. However, the major limitations of using these materials for biomedical applications are their cytotoxic effects and cellular uptake efficiency. The morphology of GdNPs, such as size, charge, and surface play an important role in affecting biocompatibility and cellular uptake. For instance, by modifying the surface of nanoparticles, the physical-chemical properties can be altered, leading to improvement in biocompatibility and cellular uptake. Various molecules have the potential to be functionalized on GdNPs, but it is essential to select those that can effectively enhance their abilities. Therefore, this review aims to discuss several studies on the effect of morphology and surface modification of GdNPs to improve biocompatibility and cellular uptake. HIGHLIGHTS Biocompatibility and uptake challenges: Size, surface charge, and functionalization of gadolinium nanoparticles (GdNPs) directly affect cellular uptake and biocompatibility, which are essential for safe and effective Magnetic Resonance Imaging (MRI) contrast. Surface modification: The review emphasizes surface modification strategies to enhance biocompatibility and cellular uptake. Functionalization with various molecules tailors GdNPs' physicochemical properties for optimized performance. Implications for design: A detailed examination of studies on morphology and modification approaches reveals pathways to improve GdNPs efficacy and safety in medical imaging. GRAPHICAL ABSTRACT