Photothermal nanofibres enable safe engineering of therapeutic cells

Photothermal nanofibres enable safe engineering of therapeutic cells
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DOI:
10.1038/s41565-021-00976-3
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发表时间:
2021
影响因子:
38.3
通讯作者:
Fra
Fra
中科院分区:
材料科学1区
文献类型:
--
作者:
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;Fra

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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.