Injectable hyaluronic acid-based hydrogels with carbon dots and an iron complex for embolization

Abstract

Although transarterial chemoembolization is a prevalent treatment for hepatocellular carcinoma (HCC), its efficacy is limited by inadequate vascular infiltration, inconsistent embolization, and lack of therapeutic synergy. We developed a multifunctional injectable hydrogel system using strategically combined high- and low-molecular-weight hyaluronic acid and a carbon dot/iron complex (APIO/Fe complex) to overcome these challenges. The dual-molecular-weight approach optimizes both structural integrity and injectability and also enables the homogeneous distribution of therapeutic agents. The APIO carbon dots were produced by a one-pot hydrothermal synthesis using iohexol and 1-(3-aminopropyl) imidazole as dual-purpose precursors for computed tomography (CT) imaging and iron chelation. The APIO/Fe complex was characterized via dynamic light scattering, X-ray photoelectron spectroscopy, and transmission electron microscopy, confirming its nanoscale structure and compositional integrity. The APIO/Fe hydrogel demonstrated shear-thinning and self-healing properties, injectability, and mechanical recovery. The APIO/Fe complex and the hydrogel preserved CT and magnetic resonance imaging contrast capabilities compared with conventional contrast agents. They also catalyzed the Fenton reaction, initiated the formation of reactive oxygen species, and accelerated coagulation upon interaction with blood. In a three-dimensional vascular model, the APIO/Fe complex induced occlusion. This multifunctional platform integrates imaging visibility, oxidative therapy, and embolic function, thus providing a synergistic, minimally invasive approach for HCC treatment.