4.8 Article

Rolling microneedle electrode array (RoMEA) empowered nucleic acid delivery and cancer immunotherapy

期刊

NANO TODAY
卷 36, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2020.101017

关键词

Electroporation; Microneedle; siRNA; CpG; Cancer immunotherapy

资金

  1. National Natural Science Foundation of China [31901053, 31871003, 91323304, 81402863, 62004007]
  2. National Key Research and Development Program of China [2016YFA0200802]
  3. Beijing Institute of Technology Research Fund Program for Young Scholars [2018CX01023]
  4. Fundamental Research Funds for the Central Universities [2018CX01023]
  5. Hunan Provincial Natural Science Foundation of China [2018JJ1019, 2019JJ50196]
  6. Hu-Xiang Young Talent Program [2018RS4094]
  7. China Postdoctoral Science Foundation Grant [2019M660309]
  8. Young Elite Scientist Sponsorship Program of Beijing Association for Science and Technology

向作者/读者索取更多资源

Topical administration of siRNA is a promising therapeutic modality, and RoMEA, an engineered rolling microneedle electrode array, enables efficient and extensive siRNA therapy. The use of RoMEA leads to effective siRNA delivery and gene silencing.
Topical administration of siRNA, a clinically approved promising therapeutic modality, represents a much more transformative approach for drug development, compared to intravenous injection. To implement an efficient and extensive siRNA therapy in vivo, we engineered a rolling microneedle electrode array (RoMEA), which utilizes parallel circular blades with microneedle arrays on edge as electrodes. RoMEA integrates close-spaced microneedle electrodes and rolling structure to allow low-damage and large-area siRNA transfection. Upon applying RoMEA, regular micropores were established, efficient siRNA delivery and gene silence were achieved. In addition, employments of siRNA targeting programmed death-ligand 1 (PD-L1) alone, or combined with anti-programmed death-1 (PD-1) antibody or immunoadjuvant of CpG2395, in two tumor xenograft murine models demonstrated that proposed strategies restored efficient T cell immune response, conferring significant tumor growth inhibition with excellent safety profiles. RoMEA constitutes an unprecedented and ingenious clinic solution to large-area local delivery of nucleic acid for cancer immunotherapy. (C) 2020 Elsevier Ltd. All rights reserved.

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