Rational design of temperature-sensitive blood-vessel-embolic nanogels for improving hypoxic tumor microenvironment after transcatheter arterial embolization

Transcatheter arterial embolization (TAE) plays an important role in clinical tumor therapy by accomplishing vessel-casting embolization of tumor arteries at all levels and suppressing tumor collateral circulation and vascular re-canalization. In this study, we describe smart blood-vessel-embolic nanogels for improving the anti-tumor efficacy of TAE therapy on hepatocellular carcinoma (HCC). Methods: In this study, an in vitro model composed of two microfluidic chips was used for simulating the tumor capillary network and analyzing artery-embolization properties. Also, blood-vessel-casting embolization of renal arteries was evaluated in normal rabbits. Using a VX2 tumor-bearing rabbit model, the therapeutic efficacy of TAE on HCC was investigated for tumor growth, necrosis, and proliferation. Neovascularization and collateral circulation were evaluated by immunofluorescent detection of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and CD31 following the TAE therapy of VX2 tumor-bearing rabbits. Results: Sufficient embolization of all eight levels of micro-channels was achieved in a tumor-vessel-mimetic model with two microfluidic chips using PIBI-2240, and was further confirmed in renal arteries of normal rabbit. Effective inhibition of tumor collateral circulation and vascular re-canalization was observed in VX2 tumor-bearing rabbits due to the reduced expression levels of HIF-1α, VEGF, and CD31. Conclusions: The exceptional anti-tumor effect of PIBI-2240 observed in this study suggested that it is an excellent blood-vessel-embolic material for tumor TAE therapy.