title: Temporal and spatial patterning of transgene expression by near-infrared irradiation.
abstract: We investigated whether near-infrared (NIR) light could be employed for patterning transgene expression in plasmonic cell constructs. Hollow gold nanoparticles with a plasmon surface band absorption peaking at ∼750 nm, a wavelength within the so called "tissue optical window", were used as fillers in fibrin-based hydrogels. These composites, which efficiently transduce NIR photon energy into heat, were loaded with genetically-modified cells that harbor a heat-activated and ligand-dependent gene switch for regulating transgene expression. NIR laser irradiation in the presence of ligand triggered 3-dimensional patterns of transgene expression faithfully matching the illuminated areas of plasmonic cell constructs. This non-invasive technology was proven useful for remotely controlling in vivo the spatiotemporal bioavailability of transgenic vascular endothelial growth factor. The combination of spatial control by means of NIR irradiation along with safe and timed transgene induction presents a high application potential for engineering tissues in regenerative medicine scenarios.
authors: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.|Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain.
authors: Francisco M
authors: FM
authors: Martin-Saavedra
authors: Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.
authors: Virginia
authors: V
authors: Cebrian
authors: Department of Chemical Engineering, Nanoscience Institute of Aragon (INA), University of Zaragoza, 50018 Zaragoza, Spain.
authors: Leyre
authors: L
authors: Gomez
authors: Institute of Polymer Science and Technology (ICTP-CSIC), 28006 Madrid, Spain.
authors: Daniel
authors: D
authors: Lopez
authors: Department of Chemical Engineering, Nanoscience Institute of Aragon (INA), University of Zaragoza, 50018 Zaragoza, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.
authors: Manuel
authors: M
authors: Arruebo
authors: Center for Craniofacial Regeneration and Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors: Christopher G
authors: CG
authors: Wilson
authors: Center for Craniofacial Regeneration and Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors: Renny T
authors: RT
authors: Franceschi
authors: Department of Physiological Sciences, University of Florida, Gainesville, FL 32611, USA.|HSF Pharmaceuticals S.A., 1814 La Tour-de-Peilz, Switzerland.
authors: Richard
authors: R
authors: Voellmy
authors: Department of Chemical Engineering, Nanoscience Institute of Aragon (INA), University of Zaragoza, 50018 Zaragoza, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.
authors: Jesus
authors: J
authors: Santamaria
authors: Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain.|CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.
authors: Nuria
authors: N
authors: Vilaboa
mesh_terms: D000818:Animals; D002470:Cell Survival; D005337:Fibrin / Q000737:chemistry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D015316:Genetic Therapy / Q000379:methods; D006046:Gold / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007259:Infrared Rays; D008024:Ligands; D008027:Light; D051379:Mice; D008809:Mice, Inbred C3H; D017348:Microscopy, Electron, Scanning Transmission; D017785:Photons; D044968:Regenerative Medicine / Q000379:methods*; D012212:Rheology; D020123:Sirolimus / Q000737:chemistry; D013997:Time Factors; D054457:Tissue Scaffolds; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020100:Hydrogels; D008024:Ligands; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D006046:Gold; D005337:Fibrin; D020123:Sirolimus
keywords: Fibrin; Gene therapy; Gold; Hydrogel; Infrared spectrum; Scaffold