Two‐Photon Light Trigger siRNA Transfection of Cancer Cells Using Non‐Toxic Porous Silicon Nanoparticles

Author:

Chaix Arnaud1,Cueto‐Diaz Eduardo1,Dominguez‐Gil Sofia1,Spiteri Chantelle23,Lichon Laure4,Maynadier Marie5,Dumail Xavier1,Aggad Dina4,Delalande Anthony678,Bessière Aurélie1,Pichon Chantal678,Chiappini Ciro23,Sailor Michael J.9,Bettache Nadir4,Gary‐Bobo Magali4,Durand Jean‐Olivier1ORCID,Nguyen Christophe4,Cunin Frédérique1

Affiliation:

1. ICGM CNRS ENSCM University of Montpellier Montpellier 34293 France

2. Centre for Craniofacial and Regenerative Biology King's College London London SE1 9RT UK

3. London Centre for Nanotechnology King's College London London WC2R 2LS UK

4. IBMM Univ. Montpellier CNRS ENSCM Montpellier 34093 France

5. NanoMedSyn Avenue Charles Flahault Montpellier Cedex 05 34093 France

6. Centre de Biophysique Moléculaire CNRS UPR4301 Orléans cedex 02 F‐45071 France

7. Inserm UMS 55 ART ARNm and University of Orléans Orléans F‐45100 France

8. Institut Universitaire de France 1 rue Descartes Paris F‐75035 France

9. University of California San Diego Department of Chemistry and Biochemistry 9500 Gilman Drive, m/c 0358 La Jolla CA 92093 USA

Abstract

AbstractThe concept of using two‐photon excitation in the NIR for the spatiotemporal control of biological processes holds great promise. However, its use for the delivery of nucleic acids has been very scarcely described and the reported procedures are not optimal as they often involve potentially toxic materials and irradiation conditions. This work prepares a simple system made of biocompatible porous silicon nanoparticles (pSiNP) for the safe siRNA photocontrolled delivery and gene silencing in cells upon two‐photon excitation. PSiNP are linked to an azobenzene moiety, which possesses a lysine group (pSiNP@ICPES‐azo@Lys) to efficiently complex siRNA. Non‐linear excitation of the two‐photon absorber system (pSiNP) followed by intermolecular energy transfer (FRET) to trans azobenzene moiety, result in the photoisomerization of the azobenzene from trans to cis and in the destabilization of the azobenzene‐siRNA complex, thus inducing the delivery of the cargo siRNA to the cytoplasm of cells. Efficient silencing in MCF‐7 expressing stable firefly luciferase with siRNAluc against luciferase is observed. Furthermore, siRNA against inhibitory apoptotic protein (IAP) leads to over 70% of MCF‐7 cancer cell death. The developed technique using two‐photon light allows a unique high spatiotemporally controlled and safe siRNA delivery in cells in few seconds of irradiation.

Funder

Agence Nationale de la Recherche

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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