The immune-chemo-embolization effect of temperature sensitive gold nanomedicines against liver cancer  

作　　者：Yiming Liu Dingwen Shi Yanqiao Ren Ling Li Yanbing Zhao Chuansheng Zheng Xiangliang Yang 

机构地区：[1]Department of Radiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China [2]National Engineering Research Center for Nanomedicine,Key Laboratory of Molecular Biophysics of Ministry of Education,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China [3]School of Biomedical Engineering,Hubei University of Science and Technology,Xianning 437100,China [4]Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica,Hubei Engineering Research Center for Biomaterials and Medical Protective Materials,Huazhong University of Science and Technology,Wuhan 430074,China [5]GBA Research Innovation Institute for Nanotechnology,Guangzhou 510530,China [6]Hubei Province Key Laboratory of Molecular Imaging,Wuhan 430022,China

出　　处：《Nano Research》2023年第2期2749-2761,共13页纳米研究（英文版）

基　　金：supported by the National Basic Research Program of China(Nos.2020YFA0710700 and 2018YFA0208900);the National Natural Science Foundation of China(Nos.82172758,81873919,and 81801810).

摘　　要：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.

关 键 词：temperature sensitive nanogels gold nanoparticles transcatheter arterial chemo-embolization(TACE) antitumor immune response 

分 类 号：R730.51[医药卫生—肿瘤]