: Today, efficient delivery of sorafenib to hepatocellular carcinoma remains a challenge for current drug formulation strategies. Incorporating the lipophilic molecule into biocompatible and biodegradable theranostic nanocarriers has great potential for improving the efficacy and safety of cancer therapy. In the present study, three different technologies for the encapsulation of sorafenib into poly(d,l-lactide-co-glycolide) and polyethylene glycol-poly(d,l-lactide-co-glycolide) copolymers were compared. The particles ranged in size between 220 and 240 nm, with encapsulation efficiencies from 76.1 ± 1.7% to 69.1 ± 10.1%. A remarkable maximum drug load of approximately 9.0% was achieved. Finally, a gadolinium complex was covalently attached to the nanoparticle surface, transforming the nanospheres into theranostic devices, allowing their localization using magnetic resonance imaging. The manufacture of sorafenib-loaded nanoparticles alongside the functionalization of the particle surface with gadolinium complexes resulted in a highly efficacious nanodelivery system which exhibited a strong magnetic resonance imaging signal, optimal stability features, and a sustained release profile.
