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Integrated Nanorod-Mediated PD-L1 Downregulation in Combination with Oxidative-Stress Immunogene Therapy against Cancer.
Wu, Shuaiying; Zhang, Jianzhong; Pan, Jie; Bai, Shuang; Wang, Ziying; Chen, Yulun; Xu, Dazhuang; An, Yibo; Liu, Chao; Chu, Chengchao; Dai, Qixuan; Jiang, Lai; Lu, Zhixiang; Liu, Gang.
Affiliation
  • Wu S; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Zhang J; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Pan J; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Bai S; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Wang Z; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Chen Y; School of Medicine, Xiamen University, Xiamen, 361102, China.
  • Xu D; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • An Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Liu C; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Chu C; School of Medicine, Xiamen University, Xiamen, 361102, China.
  • Dai Q; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Jiang L; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Lu Z; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
  • Liu G; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
Adv Healthc Mater ; 12(17): e2300110, 2023 07.
Article in En | MEDLINE | ID: mdl-36773310
It is an engaging program for tumor treatment that rationalizes the specific microenvironments, activation of suppressed immune system (immune resistance/escape reversion), and synergistic target therapy. Herein, a biomimetic nanoplatform that combines oxidative stress with genetic immunotherapy to strengthen the therapeutic efficacy is developed. Ru-TePt nanorods, small interfering RNA (PD-L1 siRNA), and biomimetic cellular membrane vesicles with the targeting ability to design a multifunctional Ru-TePt@siRNA-MVs system are rationally integrated. Notably, the Fenton-like activity significantly enhances Ru-TePt nanorods sonosensitization, thus provoking stronger oxidative stress to kill cells directly. Meanwhile, immunogenic cell death is triggered to secrete numerous cytokines and activate T cells. The effective catalase characteristics of Ru-TePt enable the in situ oxygen-producing pump to improve tumor oxygen level and coordinately strengthen the therapeutic effect of SDT followed. More importantly, anti-PD-L1-siRNA mediated immune checkpoint silence of the PD-L1 gene creates an environment conducive to activating cytotoxic T lymphocytes, synergistic with boosted reactive oxygen species-triggered antitumor immune response. The experimental results in vitro and in vivo reveal that the Ru-TePt@siRNA-MVs nanosystems can effectively activate the oxidative stress-triggered immune response and inhibit PD-1/PD-L1 axis-mediated immune resistance. Consequently, this orchestrated treatment paradigm provides valuable insights for developing potential oxidative stress and genetic immunotherapy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Immunotherapy / Neoplasms Limits: Humans Language: En Journal: Adv Healthc Mater Year: 2023 Document type: Article Affiliation country: China Country of publication: Germany

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Immunotherapy / Neoplasms Limits: Humans Language: En Journal: Adv Healthc Mater Year: 2023 Document type: Article Affiliation country: China Country of publication: Germany