详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

Synergistic Ultrasound-Activable Artificial Enzyme and Precision Gene Therapy to Suppress Redox Homeostasis and Malignant Phenotypes for Controllably Combating Hepatocellular Carcinoma

文献详情

资源类型：

Pubmed体系：

收录情况： ◇ 自然指数

作者：

机构： [1]Department of General Surgery, Liver Transplant Center, Transplant Center, Laboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China. [2]College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. [3]Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, China. [4]Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu 610093, China. [5]School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 641400, China. [6]Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin 14195, Germany. [7]Department of Endodontics, Department of Orthodontics, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

出处：

DOI：

ISSN：

摘要：

Hepatocellular carcinoma (HCC) remains one of the most lethal malignant tumors. Multimodal therapeutics with synergistic effects for treating HCC have attracted increasing attention, for instance, designing biocompatible porphyrin-based nanomedicines for enzyme-mimetic and ultrasound (US)-activable reactive oxygen species (ROS) generation. Despite the promise, the landscape of such advancements remains sparse. Here, we propose the de novo design of a π-conjugated, osmium (Os)-coordinated polyporphyrin (P-Por-Os) nanovesicle to serve as an ultrasound-activable artificial enzyme for synergistic therapies to suppress redox homeostasis and malignant phenotypes for controllably combating HCC. Our findings reveal that the P-Por-Os with US showed superior, multifaceted, and controllable ROS-generating activities. This system not only subverts the redox balance within HCC cells but also achieves precise and controlled tumor ablation at remarkably low concentrations, as evidenced across cellular assays and animal models. In the liver orthotopic model, US not only activates the artificial enzyme to catalyze ROS but also facilitates remote-controlled ablation of HCC through precise US positioning. Moreover, the P-Por-Os + US can assist the precision gene therapy by knocking down the ROS resistance factor, MT2A, and down-regulating its downstream oncogene IGFBP2 to attenuate ROS resistance, proliferation, and migration of HCC efficiently. We suggest that the design of this ultrasound-activable artificial enzyme presents a promising avenue for the engineering of innovative tumoricidal materials, offering a synergistic therapeutic approach with high biosecurity for HCC treatment.

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2024]版：

无

最新[2023]版：

大类 | 1 区

化学

小类 | 1 区化学：综合

第一作者：

第一作者机构： [1]Department of General Surgery, Liver Transplant Center, Transplant Center, Laboratory of Hepatic AI Translation, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.

共同第一作者：

通讯作者：

通讯机构： [2]College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. [6]Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin 14195, Germany. [7]Department of Endodontics, Department of Orthodontics, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

推荐引用方式(GB/T 7714)：

APA：

MLA：