Thrombin-conjugated cationic nanogels loaded with CpG enhance tumor vessel infarction by interpenetrating double gel network and immune activation.

Tumor vascular infarction (TVI) has emerged as a promising antitumor strategy by inducing specifical thrombosis in tumor-feeding arteries. Owing to blood clot degradation and the off-target effect of procoagulant, unfortunately, the recanalization or disseminated intravascular coagulation (DIC) inevitably occurred in clinical application, provoking serious side effect and rapid tumor relapse/metastasis. Herein, thrombin-conjugated poly(N-isopropylacrylamide-co-2-(diethylamino)ethyl methacrylate-co-N-acryloxysuccinimide) nanogels loaded with an immunoadjuvant CpG (c-IDTs) were constructed to exert the anti-tumor immune response for enhancing the efficacy of TVI. With the formation of interpenetrating double gel network between hydrogel of thermosensitive sol-gel transition and blood clots of thrombin-induced coagulation cascade, c-IDT nanogels achieved a long-term embolization for enhancing TVI therapy. What`s more, the generation of tumor-associated antigens (TAAs) made an antigen reservoir, which improved maturation of DCs and promoted presentation to CD8+ T cells by released immunoadjuvant (CpG), thus enhanced anti-tumor immune response for improving TVI therapy. In summary, the injectable c-IDT nanogels used for coagulation and immune-enhancing with good biocompatibility and biosafety should be developed for further biological applications.