Heat-induced manganese-doped magnetic nanocarriers combined with Yap-siRNA for MRI/NIR-guided mild photothermal and gene therapy of hepatocellular carcinoma
机构:[1]Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Key Laboratory of Thin Film and Microfabrication Technology (Ministry of Education), 800 Dongchuan Rd, Shanghai 200240, China[2]Department of Radiation Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China[3]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]Jinan Jiyang District Hospital of Traditional Chinese Medicine, Jinan, Shandong 251400, China[5]Medical Affairs, ICON PLC, Beijing, China
Over last decades, the complexity and variability of hepatocellular carcinoma (HCC) has significantly interfered with the effectiveness of traditional treatment, and has gradually become a main obstacle and bottleneck for HCC therapy. In order to explore the innovative therapeutic strategy to further improve the cancer diagnosis and treatment, we herein proposed a thermal-induced magnetic nanosystem with good biocompatibility that therapeutic cargo controllable release relies on 808 nm laser irradiation. This nanosystem was designed by co-loaded the manganese-doped magnetic nanoparticles and photosensitizer indocyanine green into the matrix of temperature sensitive polymer, with further capturing negatively charged YAP1 siRNA on the surface, to finally obtain the heat-induced manganese-doped magnetic nanocarriers (HMM-siRNA NCs). Our study found that the photosensitizer on the exposure of 808 nm laser irradiation could generate continuous heat to rupture the thermal-sensitive polymer matrix, that controllable release the embedded ICG and Mn0.8Fe2.2O4 NPs for NIR/MR imaging, ICG-mediated heat and ROS could induce the thermal expansion and rupture of HMM-siRNA NCs, causing the evident thermal swelling of lysosomes to induce the cell apoptosis. Besides, YAP1 siRNA can decrease the YAP1 expression in HCC down to approximately 35%, reducing the cell proliferation and migration. Such NIR/MRI guided low-temperature PTT and siRNA-mediated gene therapy strategy lead to tumor cell death by using various and complementary approach, thereby achieving controllable and effective comprehensive treatment in the presence of 808 nm laser irradiation. Our designed delivery complex can accomplish the precise cancer treatment on the tumor site by responding to the external 808 nm laser, and its non-toxic metabolites demonstrate the excellent biocompability for extensive use either anti-cancer therapy or various disease from clinical research.
基金:
National Key Research and Development Program of China (No. 2017FYA0205301), Projects of International Cooperation and Exchanges NSFC (No. 82020108017), National Natural Science Foundation of China (No. 81903169), Shanghai Sailing Program (No. 19YF1422300), Startup Fund for Youngman Research at SJTU (No.18X100040044), SJTU “Transformation Medicine Cross Research Fund” (No. ZH2018QNB25 and ZH2018QNB26), as well as the funding from Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument (No.15DZ2252000).
第一作者机构:[1]Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Key Laboratory of Thin Film and Microfabrication Technology (Ministry of Education), 800 Dongchuan Rd, Shanghai 200240, China
通讯作者:
通讯机构:[1]Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Key Laboratory of Thin Film and Microfabrication Technology (Ministry of Education), 800 Dongchuan Rd, Shanghai 200240, China[*1]Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China
推荐引用方式(GB/T 7714):
Zhang Qian,Zhao Weiyong,Cheng Jin,et al.Heat-induced manganese-doped magnetic nanocarriers combined with Yap-siRNA for MRI/NIR-guided mild photothermal and gene therapy of hepatocellular carcinoma[J].CHEMICAL ENGINEERING JOURNAL.2021,426:doi:10.1016/j.cej.2021.130746.
APA:
Zhang, Qian,Zhao, Weiyong,Cheng, Jin,Deng, Zhoufeng,Zhang, Ping...&Cui, Daxiang.(2021).Heat-induced manganese-doped magnetic nanocarriers combined with Yap-siRNA for MRI/NIR-guided mild photothermal and gene therapy of hepatocellular carcinoma.CHEMICAL ENGINEERING JOURNAL,426,
MLA:
Zhang, Qian,et al."Heat-induced manganese-doped magnetic nanocarriers combined with Yap-siRNA for MRI/NIR-guided mild photothermal and gene therapy of hepatocellular carcinoma".CHEMICAL ENGINEERING JOURNAL 426.(2021)