Light triggered nanoscale biolistics for efficient intracellular delivery of functional macromolecules in mammalian cells

Juan C. Fraire, Elnaz Shaabani, Maryam Sharifiaghdam, Matthias Rombaut, Charlotte Hinnekens, Dawei Hua, Jana Ramon, Laurens Raes, Eduardo Bolea-Fernandez, Toon Brans, Frank Vanhaecke, Peter Borghgraef, Chaobo Huang, Félix Sauvage, Tamara Vanhaecke, Joery Kock, Ranhua Xiong (), Stefaan Smedt () and Kevin Braeckmans ()
Additional contact information
Juan C. Fraire: Ghent University
Elnaz Shaabani: Ghent University
Maryam Sharifiaghdam: Ghent University
Matthias Rombaut: Vrije Universiteit Brussel (VUB)
Charlotte Hinnekens: Ghent University
Dawei Hua: Ghent University
Jana Ramon: Ghent University
Laurens Raes: Ghent University
Eduardo Bolea-Fernandez: Ghent University
Toon Brans: Ghent University
Frank Vanhaecke: Ghent University
Peter Borghgraef: VIB Bioimaging Core Ghent, VIB
Chaobo Huang: Nanjing Forestry University (NFU)
Félix Sauvage: Ghent University
Tamara Vanhaecke: Vrije Universiteit Brussel (VUB)
Joery Kock: Vrije Universiteit Brussel (VUB)
Ranhua Xiong: Ghent University
Stefaan Smedt: Ghent University
Kevin Braeckmans: Ghent University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Biolistic intracellular delivery of functional macromolecules makes use of dense microparticles which are ballistically fired onto cells with a pressurized gun. While it has been used to transfect plant cells, its application to mammalian cells has met with limited success mainly due to high toxicity. Here we present a more refined nanotechnological approach to biolistic delivery with light-triggered self-assembled nanobombs (NBs) that consist of a photothermal core particle surrounded by smaller nanoprojectiles. Upon irradiation with pulsed laser light, fast heating of the core particle results in vapor bubble formation, which propels the nanoprojectiles through the cell membrane of nearby cells. We show successful transfection of both adherent and non-adherent cells with mRNA and pDNA, outperforming electroporation as the most used physical transfection technology by a factor of 5.5–7.6 in transfection yield. With a throughput of 104-105 cells per second, biolistic delivery with NBs offers scalable and highly efficient transfections of mammalian cells.

Date: 2022
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DOI: 10.1038/s41467-022-29713-7

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