Ultrasound-driven in situ self-assembly of drug hydrogel for enhanced hepatic artery infusion chemotherapy

Hepatic arterial infusion chemotherapy (HAIC) delivers high local drug concentrations for hepatoma treatment but faces challenges such as catheter-related complications and systemic toxicity. To address these, we developed Mel-gel, an ultrasound-driven hydrogel system formed entirely by the chemotherapeutic agent Melphalan (Mel) without chemical modifications. Under ultrasound, Mel transitions from spherical to worm-like aggregates, rapidly forming a nanofiber-based hydrogel through non-covalent interactions. This innovative system offers sustained drug release, excellent bioavailability, and improved biosafety profiles. Mel-gel enables expedited catheter removal, reduces systemic toxicity, enhances local drug concentration, and prolongs drug-cell interaction time. Compared to conventional HAIC systems, Mel-gel’s unique in situ formation maximizes drug delivery and achieves superior targeting within complex vascular structures. In a rat orthotopic hepatoma model, Mel-gel-assisted HAIC demonstrated remarkable therapeutic efficacy, achieving a tumor inhibition rate of 98.09%, activating anti-tumor immune responses, and curing 60% of treated rats. This novel ultrasound-responsive hydrogel represents a promising advancement in hepatoma treatment, offering enhanced precision, efficacy, and safety. Additionally, Mel-gel’s versatile drug delivery capabilities may enhance the pharmacokinetics of various drugs and support synergistic therapies. This novel hydrogel system offers a promising advancement in hepatoma treatment, aiming to optimize outcomes and expand its application to other therapeutic agents.