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Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer.
Huang, Kuan-Wei; Hsu, Fu-Fei; Qiu, Jiantai Timothy; Chern, Guann-Jen; Lee, Yi-An; Chang, Chih-Chun; Huang, Yu-Ting; Sung, Yun-Chieh; Chiang, Cheng-Chin; Huang, Rui-Lin; Lin, Chu-Chi; Dinh, Trinh Kieu; Huang, Hsi-Chien; Shih, Yu-Chuan; Alson, Donia; Lin, Chun-Yen; Lin, Yung-Chang; Chang, Po-Chiao; Lin, Shu-Yi; Chen, Yunching.
Afiliación
  • Huang KW; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Hsu FF; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Qiu JT; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Chern GJ; Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Lee YA; Department of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Chang CC; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Huang YT; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Sung YC; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Chiang CC; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County 35053, Taiwan.
  • Huang RL; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Lin CC; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Dinh TK; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Huang HC; Department of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Shih YC; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Alson D; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Lin CY; Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • Lin YC; Department of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Chang PC; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Lin SY; Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center; Chang Gung Memorial Hospital, Taoyuan, Taiwan.
  • Chen Y; Division of Medical Oncology/Hematology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Sci Adv ; 6(3): eaax5032, 2020 01.
Article en En | MEDLINE | ID: mdl-31998834
ABSTRACT
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Nanopartículas / Fenómenos Inmunogenéticos / Terapia Molecular Dirigida / Nanomedicina Teranóstica / Neoplasias Límite: Animals / Humans / Male Idioma: En Revista: Sci Adv Año: 2020 Tipo del documento: Article País de afiliación: Taiwán
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Nanopartículas / Fenómenos Inmunogenéticos / Terapia Molecular Dirigida / Nanomedicina Teranóstica / Neoplasias Límite: Animals / Humans / Male Idioma: En Revista: Sci Adv Año: 2020 Tipo del documento: Article País de afiliación: Taiwán