國家衛生研究院 NHRI:Item 3990099045/12507
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    题名: Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer
    作者: Huang, KW;Hsu, FF;Qiu, JTT;Chern, GJ;Lee, YA;Chang, CC;Huang, YT;Sung, YC;Chiang, CC;Huang, RL;Lin, CC;Dinh, TK;Huang, HC;Shih, YC;Alson, D;Lin, CY;Lin, YC;Chang, PC;Lin, SY;Chen, YC
    贡献者: Institute of Biomedical Engineering and Nanomedicine
    摘要: While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)-cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8(+) T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.
    日期: 2020-01
    關聯: Science Advances. 2020 Jan;6(3):Article number eaax5032.
    Link to: http://dx.doi.org/10.1126/sciadv.aax5032
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2375-2548&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000507562700003
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85078092406
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