English
Transcatheter arterial embolization (TAE) is the preferred treatment for unresectable advanced hepatocellular carcinoma (HCC) patients and is minimally invasive. However, due to the lack of ideal embolic agents, its therapeutic effect is limited by incomplete occlusion of the entire tumor vascular system and intensified tumor immune suppression. Here, thrombin was loaded onto calcium carbonate (CaCO) nanoparticles embedded in gelatin microspheres (Th CaCO @ gelatin MS) through a microfluidic process, and size adjustable procoagulant embolization microspheres were prepared. In this system, the generated Th CaO @ gelatin MS can occlude the main tumor blood supply vessels, while the acidic tumor microenvironment triggers the release of thrombin and Ca, which can synergistically promote the formation of intravascular thrombosis to occlude tumor capillaries. Meanwhile, the embedded CaCO nanoparticles can act as proton sponges to neutralize the acidity of tumors, effectively reversing tumor immune suppression. Therefore, TAE treatment with Th CaCO @ gelatin MS showed the most effective tumor suppression effect on in situ N1S1 HCC rat xenografts, without causing significant toxic effects. Therefore, this study emphasizes that our biocompatible embolic microspheres have great potential for clinical translation by enhancing conventional TAE therapy by promoting pH responsive tumor vascular infarction and neutralizing acidic tumor microenvironment.
