The immune-chemo-embolization effect of temperature sensitive gold nanomedicines against liver cancer
Yiming Liu, Dingwen Shi, Yanqiao Ren, Ling Li, Yanbing Zhao, Chuansheng Zheng, Xiangliang Yang
Abstract
Although transcatheter arterial chemo-embolization (TACE) plays a key role on clinical treatment of hepatocellular carcinoma (HCC), it was greatly limited by the poor synergistic effect between chemotherapeutics and physical embolization to tumor-feeding arteries. In the present work, a temperature sensitive polymer poly(N-isopropylacrylamide-b-methacrylic acid) (PNA), which was modified with gold nanoparticles (AuNP@PNA), was successfully used to encapsulate doxorubicin (DOX) by electrostatic binding with their carboxyl groups. The resultant gold nanomedicines (AuNP@PNA/DOX) exhibited temperature responsive sol-gel phase transition, favorable shear thinning effect and X-ray angiography. By in vivo evaluation of vascular embolization on VX2-tumor-bearing rabbits, AuNP@PNA/DOX exhibited far better antitumor efficacy than Lipiodol/DOX, on either tumor growth inhibition, proliferation, apoptosis, necrosis or anti-metastasis. Owing to sufficient embolization to tumor vascular networks, AuNP@PNA/DOX down-regulated the expression levels of HIF-1α, VEGF and MMP-9, and prompted more efficient activation on CD3+/CD8+ T cells and the related cytokines, suggesting the synergistic effect between AuNP@PNA and DOX on the improvement of post-operative tumor immunosuppressive microenvironment. With their favorable pharmcokinetics and biocompatibility, AuNP@PNA/DOX is promising to be developed as a multi-functional artery-imaging/embolic agent with immune-chemo-embolization for enhancing TACE efficacy on HCC.