A gradient core-shell microsphere to enable effective embolization of liver cancer via interventional therapy

Embolic microspheres are important for the interventional treatment of solid tumors, but it is a dilemma for microspheres to keep sufficient strength and resilience. Herein, we propose a strategy to fabricate core-shell poly(vinyl alcohol) microspheres with gradient crosslinking (GCL) on an industrial scale to solve the dilemma. The synthesized GCL microspheres exhibit superior mechanical characteristics in comparison to the homogeneous microspheres and the conventional core-shell microspheres produced by standard one-step and two-step methods, respectively. An in vitro model is conducted to assess the distribution in the vascular network and migration over time of three microspheres. The GCL microspheres possess optimal strength and flexibility, facilitating distal vascular embolization and reducing the risk of microsphere migration over time. The performances are validated in vivo with the porcine renal model in large animal experiments. Clinical trials addressing liver cancer further confirm the embolic efficacy and safety of the GCL microspheres in humans. The relationship between mechanical properties and embolic efficiency offers valuable insights for the development of other embolic agents in the formulism of interventional therapy.