Journal
NATURE NANOTECHNOLOGY
Volume 16, Issue 11, Pages 1281-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41565-021-00976-3
Keywords
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Funding
- National Natural Science Foundation of China [21774060, 21644004]
- European Research Council (ERC Consolidator Grant) [648124]
- Research Foundation Flanders (FWO) [1500418N, 12Q8718N, 1S62517N]
- National Key R&D Program of China [2017YFF0207804]
- Youth Innovation Promotion Association CAS [2018491]
- European Union's Horizon 2020 research and innovation programme [810685]
- European Research Council (ERC) [648124] Funding Source: European Research Council (ERC)
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Photothermal nanofibres embedded with iron oxide nanoparticles can deliver effector macromolecules to different types of cells without causing cellular toxicity or diminishing therapeutic potency, showing promise for safe and efficient production of engineered cells for therapeutic applications.
Nanoparticle-mediated photoporation is used to temporarily permeabilize cell membranes for intracellular delivery of macromolecules, but cell exposure to nanoparticles might cause cellular damage and hamper application of the technique to therapeutic cell engineering. Here the authors show that, under photothermal heating, nanofibre-embedded iron oxide nanoparticles can be used to deliver effector macromolecules to different types of cells, in a contactless manner, with no cellular toxicity or diminished therapeutic potency. 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.
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