Magnetic Bioadhesive for Tumor Therapy: Synergistic Magnetothermal and Chemodynamic Effects

Therapeutic bioadhesives with injectability, strong adhesion, magnetothermal responsiveness, sustained efficacy, and biosafety are desired for in situ deep-tumor eradication but remain underexplored. Here, injectable magnetic bioadhesives are developed via physical condensation of zein, poly-lysine (PLL), and Fe₃O₄ nanoparticles. Pre-encapsulated genipin within the resulting zein/PLL/Fe₃O₄ adhesives regulates covalent cross-linking both at the tissue-adhesive interface and within the matrix, enabling the adhesives to achieve self-reinforced tissue adhesion (111.7 ± 23.5 kPa) in wet physiological environments. In vitro and in vivo experiments show that Fe₃O₄'s magnetothermal property under AMF elevates local temperature, which promotes both the tumors ablation via magnetothermal therapy (MHT) and the generation of reactive oxygen species (ROS) via Fenton reaction. Conversely, the generated ROS not only achieves chemo-dynamic therapy (CDT) but also inhibits heat shock protein expression, enhancing MHT efficacy. The synchronous synergy of MHT and CDT enables potent antitumor efficacy, with tumor tissues in nude mice nearly vanishing after 2-week treatment. Additionally, strong tumor adhesion of the adhesive minimizes off-target thermal damage. Critically, protein-based magnetic bioadhesives exhibit excellent biocompatibility and slow degradation. With deep-tissue magnetic field penetration, these features enable the adhesives to serve as a reliable platform for in situ long-term antitumor therapy.