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Nat Nanotechnol. 2021 Nov;16(11):1281-1291. doi: 10.1038/s41565-021-00976-3. Epub 2021 Oct 21.

Photothermal nanofibres enable safe engineering of therapeutic cells.

Nature nanotechnology

Ranhua Xiong, Dawei Hua, Jelter Van Hoeck, Dominika Berdecka, Laurens Léger, Stijn De Munter, Juan C Fraire, Laurens Raes, Aranit Harizaj, Félix Sauvage, Glenn Goetgeluk, Melissa Pille, Jeffrey Aalders, Joke Belza, Thibaut Van Acker, Eduardo Bolea-Fernandez, Ting Si, Frank Vanhaecke, Winnok H De Vos, Bart Vandekerckhove, Jolanda van Hengel, Koen Raemdonck, Chaobo Huang, Stefaan C De Smedt, Kevin Braeckmans

Affiliations

  1. Joint Laboratory of Advanced Biomedical Materials (Nanjing Forestry University-Ghent University), International Innovation for Center for Forest Chemicals and Materials, College of Chemical Engineering, Nanjing Forestry University, Nanjing, People's Republic of China. [email protected].
  2. Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. [email protected].
  3. Joint Laboratory of Advanced Biomedical Materials (Nanjing Forestry University-Ghent University), International Innovation for Center for Forest Chemicals and Materials, College of Chemical Engineering, Nanjing Forestry University, Nanjing, People's Republic of China.
  4. Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
  5. Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
  6. Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  7. Department of Diagnostic Sciences and Cancer Research Institute Ghent, Ghent University, Ghent, Belgium.
  8. Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  9. Department of Chemistry, Atomic and Mass Spectrometry Research Group, Ghent University, Ghent, Belgium.
  10. Department of Modern Mechanics, University of Science and Technology of China, Hefei, People's Republic of China.
  11. Joint Laboratory of Advanced Biomedical Materials (Nanjing Forestry University-Ghent University), International Innovation for Center for Forest Chemicals and Materials, College of Chemical Engineering, Nanjing Forestry University, Nanjing, People's Republic of China. [email protected].
  12. Joint Laboratory of Advanced Biomedical Materials (Nanjing Forestry University-Ghent University), International Innovation for Center for Forest Chemicals and Materials, College of Chemical Engineering, Nanjing Forestry University, Nanjing, People's Republic of China. [email protected].
  13. Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. [email protected].
  14. Center for Advanced Light Microscopy, Ghent University, Ghent, Belgium. [email protected].
  15. Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. [email protected].
  16. Center for Advanced Light Microscopy, Ghent University, Ghent, Belgium. [email protected].

PMID: 34675410 PMCID: PMC7612007 DOI: 10.1038/s41565-021-00976-3

Abstract

Nanoparticle-sensitized photoporation is an upcoming approach for the intracellular delivery of biologics, combining high efficiency and throughput with excellent cell viability. However, as it relies on close contact between nanoparticles and cells, its translation towards clinical applications is hampered by safety and regulatory concerns. Here we show that light-sensitive iron oxide nanoparticles embedded in biocompatible electrospun nanofibres induce membrane permeabilization by photothermal effects without direct cellular contact with the nanoparticles. The photothermal nanofibres have been successfully used to deliver effector molecules, including CRISPR-Cas9 ribonucleoprotein complexes and short interfering RNA, to adherent and suspension cells, including embryonic stem cells and hard-to-transfect T cells, without affecting cell proliferation or phenotype. In vivo experiments furthermore demonstrated successful tumour regression in mice treated with chimeric antibody receptor T cells in which the expression of programmed cell death protein 1 (PD1) is downregulated after nanofibre photoporation with short interfering RNA to PD1. In conclusion, cell membrane permeabilization with photothermal nanofibres is a promising concept towards the safe and more efficient production of engineered cells for therapeutic applications, including stem cell or adoptive T cell therapy.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

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