Plasmonic activation of gold nanorods for remote stimulation of calcium signaling and protein expression in HEK 293T cells

Remote activation of specific cells of a heterogeneous population can provide a useful research tool for clinical and therapeutic applications. Here, we demonstrate that photostimulation of gold nanorods (AuNRs) using a tunable near‐infrared (NIR) laser at specific longitudinal surface plasmon resonance wavelengths can induce the selective and temporal internalization of calcium in HEK 293T cells. Biotin‐PEG‐Au nanorods coated with streptavidin Alexa Fluor‐633 and biotinylated anti‐His antibodies were used to decorate cells genetically modified with His‐tagged TRPV1 temperature‐sensitive ion channel and AuNRs conjugated to biotinylated RGD peptide were used to decorate integrins in unmodified cells. Plasmonic activation can be stimulated at weak laser power (0.7–4.0 W/cm2) without causing cell damage. Selective activation of TRPV1 channels could be controlled by laser power between 1.0 and 1.5 W/cm2. Integrin targeting robustly stimulated calcium signaling due to a dense cellular distribution of nanoparticles. Such an approach represents a functional tool for combinatorial activation of cell signaling in heterogeneous cell populations. Our results suggest that it is possible to induce cell activation via NIR‐induced gold nanorod heating through the selective targeting of membrane proteins in unmodified cells to produce calcium signaling and downstream expression of specific genes with significant relevance for both in vitro and therapeutic applications. Biotechnol. Bioeng. 2016;113: 2228–2240. © 2016 Wiley Periodicals, Inc.

[1]  Jonathan S. Dordick,et al.  Radio-Wave Heating of Iron Oxide Nanoparticles Can Regulate Plasma Glucose in Mice , 2012, Science.

[2]  K. Gardner,et al.  An optogenetic gene expression system with rapid activation and deactivation kinetics , 2013, Nature chemical biology.

[3]  Niklas Smedemark-Margulies,et al.  Tools, methods, and applications for optophysiology in neuroscience , 2013, Front. Mol. Neurosci..

[4]  Thomas E Cheatham,et al.  Structure-Activity Relationship of Capsaicin Analogs and Transient Receptor Potential Vanilloid 1-Mediated Human Lung Epithelial Cell Toxicity , 2011, Journal of Pharmacology and Experimental Therapeutics.

[5]  Xiaohua Huang,et al.  Applications of gold nanorods for cancer imaging and photothermal therapy. , 2010, Methods in molecular biology.

[6]  Walther Akemann,et al.  A comprehensive concept of optogenetics. , 2012, Progress in Brain Research.

[7]  M. Berridge,et al.  The versatility and universality of calcium signalling , 2000, Nature Reviews Molecular Cell Biology.

[8]  W. Akemann,et al.  Nanobiotechnology: Remote control of cells. , 2010, Nature nanotechnology.

[9]  Heng Huang,et al.  Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. , 2010, Nature nanotechnology.

[10]  M. Nelson,et al.  Calcium signaling in smooth muscle. , 2011, Cold Spring Harbor perspectives in biology.

[11]  Bernd Nilius,et al.  Pharmacology of Vanilloid Transient Receptor Potential Cation Channels , 2009, Molecular Pharmacology.

[12]  A. Szallasi,et al.  Molecular Mechanisms of TRPV1 Channel Activation , 2010 .

[13]  Hui Li,et al.  Activity-dependent targeting of TRPV1 with a pore-permeating capsaicin analog , 2011, Proceedings of the National Academy of Sciences.

[14]  John W Haycock,et al.  Laser exposure of gold nanorods can induce intracellular calcium transients , 2014, Journal of biophotonics.

[15]  Jon Dobson,et al.  Remote control of cellular behaviour with magnetic nanoparticles. , 2008, Nature nanotechnology.

[16]  M. García,et al.  Surface plasmons in metallic nanoparticles: fundamentals and applications , 2012 .

[17]  D. Clapham,et al.  Calcium signaling , 1995, Cell.

[18]  Stephan Schmidt,et al.  Mechanical strength and intracellular uptake of CaCO3-templated LbL capsules composed of biodegradable polyelectrolytes: the influence of the number of layers. , 2013, Journal of materials chemistry. B.

[19]  G. Stuart,et al.  Different Calcium Sources Control Somatic versus Dendritic SK Channel Activation during Action Potentials , 2013, The Journal of Neuroscience.

[20]  R. Treisman,et al.  Calcium Controls Gene Expression via Three Distinct Pathways That Can Function Independently of the Ras/Mitogen-Activated Protein Kinases (ERKs) Signaling Cascade , 1997, The Journal of Neuroscience.

[21]  Xiaohua Huang,et al.  Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications , 2009, Advanced materials.

[22]  Erika Pastrana,et al.  Optogenetics: controlling cell function with light , 2011, Nature Methods.

[23]  K. L. Cheung,et al.  CTAB-coated gold nanorods elicit allergic response through degranulation and cell death in human basophils. , 2012, Nanoscale.

[24]  Jennifer E Gagner,et al.  Effect of gold nanoparticle morphology on adsorbed protein structure and function. , 2011, Biomaterials.

[25]  Takuro Niidome,et al.  PEG-modified gold nanorods with a stealth character for in vivo applications. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[26]  K. Hamad-Schifferli,et al.  Selective release of multiple DNA oligonucleotides from gold nanorods. , 2009, ACS nano.

[27]  J. West,et al.  Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer , 2010, International journal of nanomedicine.

[28]  S. Singh,et al.  Functionalized Gold Nanoparticles and Their Biomedical Applications , 2011, Nanomaterials.

[29]  Carolyn L Bayer,et al.  Influence of nanosecond pulsed laser irradiance on the viability of nanoparticle-loaded cells: implications for safety of contrast-enhanced photoacoustic imaging , 2013, Nanotechnology.

[30]  Jeremy P. Sauer,et al.  Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles , 2014, Nature Medicine.

[31]  M. Häusser,et al.  Targeting neurons and photons for optogenetics , 2013, Nature Neuroscience.

[32]  Alaaldin M. Alkilany,et al.  Gold nanorods: their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions. , 2012, Advanced drug delivery reviews.

[33]  Michael R Hamblin,et al.  Pre-Conditioning with Low-Level Laser (Light) Therapy: Light before the Storm , 2014, Dose-response : a publication of International Hormesis Society.

[34]  Jui-Teng Lin,et al.  In vitro photothermal destruction of cancer cells using gold nanorods and pulsed-train near-infrared laser , 2012 .

[35]  M. Coppey,et al.  Subcellular control of Rac-GTPase signalling by magnetogenetic manipulation inside living cells. , 2013, Nature nanotechnology.

[36]  D. Cui,et al.  Functionalized Gold Nanorods for Tumor Imaging and Targeted Therapy , 2012, Cancer biology & medicine.

[37]  Stanislav Emelianov,et al.  Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy , 2010, Optics express.

[38]  T. Imae,et al.  Functionalization of Gold Nanorods Toward Their Applications , 2009 .

[39]  Hao Hong,et al.  Applications of gold nanoparticles in cancer nanotechnology. , 2008, Nanotechnology, science and applications.

[40]  Young Ha Kim,et al.  Photothermal Cancer Therapy and Imaging Based on Gold Nanorods , 2011, Annals of Biomedical Engineering.

[41]  Jing Wang,et al.  Gold Nanorods Based Platforms for Light-Mediated Theranostics , 2013, Theranostics.

[42]  J. Dobson,et al.  Selective activation of mechanosensitive ion channels using magnetic particles , 2007, Journal of The Royal Society Interface.

[43]  Yinan Zhang,et al.  Effect of Size, shape, and surface modification on cytotoxicity of gold nanoparticles to human HEp-2 and canine MDCK cells , 2012 .

[44]  L. Pagliaro,et al.  Photothermal therapy using gold nanorods and near-infrared light in a murine melanoma model increases survival and decreases tumor volume , 2014 .

[45]  John Stone,et al.  Biological applications of gold nanorods. , 2011, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[46]  D. Ingber,et al.  Ultra-rapid activation of TRPV4 ion channels by mechanical forces applied to cell surface beta1 integrins. , 2010, Integrative biology : quantitative biosciences from nano to macro.

[47]  G. Hüttmann,et al.  Bleaching of plasmon-resonance absorption of gold nanorods decreases efficiency of cell destruction. , 2012, Journal of biomedical optics.

[48]  T. Südhof,et al.  Calcium control of neurotransmitter release. , 2012, Cold Spring Harbor perspectives in biology.

[49]  J. Cheon,et al.  Artificial control of cell signaling and growth by magnetic nanoparticles. , 2010, Angewandte Chemie.

[50]  B. Roth,et al.  Remote Control of Neuronal Signaling , 2011, Pharmacological Reviews.

[51]  A. P. Leonov,et al.  Detoxification of gold nanorods by treatment with polystyrenesulfonate. , 2008, ACS nano.

[52]  Richard Su,et al.  Highly purified biocompatible gold nanorods for contrasted optoacoustic imaging of small animal models. , 2012, Nanoscience and nanotechnology letters.

[53]  B. Kornmann,et al.  Organization and function of membrane contact sites. , 2013, Biochimica et biophysica acta.

[54]  J. Putney,et al.  Store-operated calcium channels. , 2005, Physiological reviews.

[55]  F. Bezanilla,et al.  Photosensitivity of Neurons Enabled by Cell-Targeted Gold Nanoparticles , 2015, Neuron.

[56]  Christopher A. Voigt,et al.  The promise of optogenetics in cell biology: interrogating molecular circuits in space and time , 2011, Nature Methods.