VNB-mediated endosomal escape triggers robust gene silencing in human cell lines

Juan C. Fraire; Gaëlle Houthaeve; Jing Liu; Laurens Raes; Stephan Stremersch; Toon Brans; Gerardo García-Díaz Barriga; Koen Raemdonck; Winnok H. De Vos; Stefaan De Smedt; Kevin Braeckmans

doi:10.1117/12.2542160

21 February 2020 VNB-mediated endosomal escape triggers robust gene silencing in human cell lines

Juan C. Fraire, Gaëlle Houthaeve, Jing Liu, Laurens Raes, Stephan Stremersch, Toon Brans, Gerardo García-Díaz Barriga, Koen Raemdonck, Winnok H. De Vos, Stefaan De Smedt, Kevin Braeckmans

Author Affiliations +

Proceedings Volume 11255, Colloidal Nanoparticles for Biomedical Applications XV; 1125504 (2020) https://doi.org/10.1117/12.2542160
Event: SPIE BiOS, 2020, San Francisco, California, United States

Abstract

Endosomal escape remains the most prominent bottleneck at the intracellular level for non-viral vectors today. Gold nanoparticles (AuNP) can be used to overcome the endosomal membrane barrier upon laser irradiation. Depending on the energy of nanosecond laser pulses, this can be achieved by either endosomal rupture by the mechanical energy from water vapor nanobubbles (VNBs) that emerge around the AuNP, or permeabilization of the endosomal membrane by heat diffusion. Here, we designed a siRNA/AuNP drug delivery system, to address the open question of how both photothermal effects influence cargo release, transfection efficiency, acute cytotoxicity and cell homeostasis. We found that, contrary to heat-mediated endosomal escape, VNB generation produced excellent transfection levels independent of the cell type, without inducing long-term changes in cell homeostasis.

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Juan C. Fraire, Gaëlle Houthaeve, Jing Liu, Laurens Raes, Stephan Stremersch, Toon Brans, Gerardo García-Díaz Barriga, Koen Raemdonck, Winnok H. De Vos, Stefaan De Smedt, and Kevin Braeckmans "VNB-mediated endosomal escape triggers robust gene silencing in human cell lines", Proc. SPIE 11255, Colloidal Nanoparticles for Biomedical Applications XV, 1125504 (21 February 2020); https://doi.org/10.1117/12.2542160

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