Synergistic Effect of Doxorubicin-Thermo-Iodized Oil Pickering Emulsions on the Interventional Embolization-Chemotherapy- Immunity of VX2 Rabbit Liver Cancer

Background: Tumor recurrence and metastasis are important factors affecting the efficacy of transhepatic arterial chemoembolization. To prolong the survival of patients, comprehensive interventional therapy and antitumor drugs that can control their release need to be developed. Methods: Poly(N-isopropylacrylamide-co-acrylic acid) nanogels are firstly self-assembled with doxorubicin, the constructed doxorubicin-loaded nanogels were then emulsified with iodized oil under high-shear conditions to form doxorubicin–iodized oil nanogel suspensions (Dox-TIPE). The structural characteristics, thermosensitive properties and rheological properties were evaluated. The in vitro biocompatibility and drug release behavior of Dox-TIPE were assayed and in vivo interventional therapy was examined in a VX2 rabbit liver cancer model. Results: Dox-TIPE can effectively exert the dual advantages of chemoembolization therapy, achieving a superior therapeutic effect on inhibiting rabbit liver tumor growth. It promotes TUNEL expression in the tumor boundary region while reducing Ki67 expression, which results in decreased tumor cell proliferation and increased apoptosis rates. Furthermore, Dox-TIPE effectively suppresses the expressions of HIF-1α, VEGF, and CD31 in tumor target areas, thereby preventing the formation of tumor neovascularization and collateral circulation. Conclusion: We successfully produced Dox-TIPE which offers a multifunctional platform combining embolization, chemotherapy, imaging, and immunomodulation. This novel embolic material shows strong potential to address current limitations of TACE in liver cancer treatment and may serve as a promising candidate for next-generation embolization therapies. The illustration depicts a medical procedure involving Dox-TIPE injection in a rabbit. On the left, a digital subtraction angiography machine is shown directing X-ray imaging towards the rabbit, highlighting the liver. The liver is illustrated with embolization effects, marked by a cluster of particles. Below the liver, text states ’ 1. Excellent embolization effect’ and ’ 2. Long-term X-ray Imaging’. On the right, a close-up view labeled ’After embolization’ shows a cluster of particles with arrows indicating changes in tumor response indicators: Ki67, TUNEL, CD4 superscript plus, CD8 superscript plus, HIF-1 subscript alpha, VEGF and CD31. Text below this section lists ’ 1. Sustained release of doxorubicin’, ’ 2. Tumor cell apoptosis induces immunogenic response’ and ’ 3. Minimize tumor collateral circulation’.Illustration of Dox-TIPE injection in a rabbit, showing embolization effects and tumor response indicators.