Cellular Uptake of Hybrid PLGA-Lipid Gadolinium Nanoparticles Functionalized for Magnetic Resonance Imaging of Pancreatic Adenocarcinoma Cells

Pancreatic adenocarcinoma (PDAC) presents significant diagnostic challenges, necessitating improved imaging techniques. Here, we develop hybrid poly-(lactic-<i>co</i>-glycolic acid) (PLGA)-phospholipid nanoparticles (NPs) loaded with gadolinium (Gd) chelates and functionalized with albumin, adenosine, or glutamine to boost their internalization in PDAC cells and increase the detectability by magnetic resonance imaging (MRI). Gd-PLGA NPs were synthesized using an <i>oil-in-water</i> emulsion solvent extraction method and incorporating DSPE-PEG(2000)-methoxy and DPPE-PEG(2000) <i>N</i>-Hydroxysuccinimide (NHS) for surface functionalization with albumin, adenosine, or glutamine. NPs were characterized by dynamic light scattering for particle size and ζ potential measurements, in addition to ¹H NMR and proton nuclear magnetic relaxation dispersion to assess relaxivity and contrastographic properties, and stability studies were conducted in both HEPES-buffered saline and human serum. Reported studies demonstrated that all the preparations display a good stability, a hydrodynamic diameter lower than 200 nm, and a slight negative surface charge, with good potential for applications in cells and in vivo. In vitro studies on MiaPaca2 and Panc1 cell lines confirmed that functionalized NPs display higher cellular uptake and stronger MRI signal enhancement than unconjugated controls, with albumin-PLGA-lipid NPs leading to the greatest uptake. Our findings highlight a promising route toward a more sensitive, targeted MRI of PDAC, calling for in vivo studies to assess diagnostic potential and therapeutic applications.