Dye-Sensitized Core/Active Shell Upconversion Nanoparticles for Optogenetics and Bioimaging Applications.

Near-infrared (NIR) dye-sensitized upconversion nanoparticles (UCNPs) can broaden the absorption range and boost upconversion efficiency of UCNPs. Here, we achieved significantly enhanced upconversion luminescence in dye-sensitized core/active shell UCNPs via the doping of ytterbium ions (Yb(3+)) in the UCNP shell, which bridged the energy transfer from the dye to the UCNP core. As a result, we synergized the two most practical upconversion booster effectors (dye-sensitizing and core/shell enhancement) to amplify upconversion efficiency. We demonstrated two biomedical applications using these UCNPs. By using dye-sensitized core/active shell UCNP embedded poly(methyl methacrylate) polymer implantable systems, we successfully shifted the optogenetic neuron excitation window to a biocompatible and deep tissue penetrable 800 nm wavelength. Furthermore, UCNPs were water-solubilized with Pluronic F127 with high upconversion efficiency and can be imaged in a mouse model.

[1]  Liangzhu Feng,et al.  Antigen-Loaded Upconversion Nanoparticles for Dendritic Cell Stimulation, Tracking, and Vaccination in Dendritic Cell-Based Immunotherapy. , 2015, ACS nano.

[2]  Wei Feng,et al.  Sub-10 nm hexagonal lanthanide-doped NaLuF4 upconversion nanocrystals for sensitive bioimaging in vivo. , 2011, Journal of the American Chemical Society.

[3]  Steven Jacques,et al.  Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue , 2015, Lasers in surgery and medicine.

[4]  Guanying Chen,et al.  Theranostic Upconversion Nanoparticles (II) , 2013, Theranostics.

[5]  Feng Zhang,et al.  Multimodal fast optical interrogation of neural circuitry , 2007, Nature.

[6]  Feng Wang,et al.  Photon Upconversion in Core—Shell Nanoparticles , 2015 .

[7]  Zhuang Liu,et al.  Upconversion nanophosphors for small-animal imaging. , 2012, Chemical Society reviews.

[8]  Dongmei Yang,et al.  Current advances in lanthanide ion (Ln(3+))-based upconversion nanomaterials for drug delivery. , 2015, Chemical Society reviews.

[9]  Yei Hwan Jung,et al.  Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics , 2013, Science.

[10]  Liang Cheng,et al.  Protein modified upconversion nanoparticles for imaging-guided combined photothermal and photodynamic therapy. , 2014, Biomaterials.

[11]  Lief E. Fenno,et al.  The development and application of optogenetics. , 2011, Annual review of neuroscience.

[12]  Warren M Grill,et al.  Implanted neural interfaces: biochallenges and engineered solutions. , 2009, Annual review of biomedical engineering.

[13]  D. Kleinfeld,et al.  ReaChR: A red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation , 2013, Nature Neuroscience.

[14]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[15]  Helmut Schäfer,et al.  Upconverting nanoparticles. , 2011, Angewandte Chemie.

[16]  Jie Shen,et al.  Lanthanide-doped upconverting luminescent nanoparticle platforms for optical imaging-guided drug delivery and therapy. , 2013, Advanced drug delivery reviews.

[17]  Xiaogang Liu,et al.  Enhancing luminescence in lanthanide-doped upconversion nanoparticles. , 2014, Angewandte Chemie.

[18]  Wei Fan,et al.  Engineering the Upconversion Nanoparticle Excitation Wavelength: Cascade Sensitization of Tri‐doped Upconversion Colloidal Nanoparticles at 800 nm , 2013 .

[19]  Ya-Wen Zhang,et al.  High-quality sodium rare-earth fluoride nanocrystals: controlled synthesis and optical properties. , 2006, Journal of the American Chemical Society.

[20]  John A Rogers,et al.  Fabrication and application of flexible, multimodal light-emitting devices for wireless optogenetics , 2013, Nature Protocols.

[21]  Jun Lin,et al.  Colloidal synthesis and remarkable enhancement of the upconversion luminescence of BaGdF5:Yb3+/Er3+ nanoparticles by active-shell modification , 2011 .

[22]  Muthu Kumara Gnanasammandhan Jayakumar,et al.  Upconversion nanoparticles as versatile light nanotransducers for photoactivation applications. , 2015, Chemical Society reviews.

[23]  M. Berns,et al.  In-depth activation of channelrhodopsin 2-sensitized excitable cells with high spatial resolution using two-photon excitation with a near-infrared laser microbeam. , 2008, Biophysical journal.

[24]  Juan Wang,et al.  Direct evidence of a surface quenching effect on size-dependent luminescence of upconversion nanoparticles. , 2010, Angewandte Chemie.

[25]  Emory M. Chan,et al.  Amplifying the Red-Emission of Upconverting Nanoparticles for Biocompatible Clinically Used Prodrug-Induced Photodynamic Therapy , 2014, ACS nano.

[26]  Jie Shen,et al.  Upconversion Nanoparticles: A Versatile Solution to Multiscale Biological Imaging , 2014, Bioconjugate chemistry.

[27]  Xiaogang Liu,et al.  Recent advances in the chemistry of lanthanide-doped upconversion nanocrystals. , 2009, Chemical Society reviews.

[28]  Shanshan Huang,et al.  Poly(Acrylic Acid) Modification of Nd3+‐Sensitized Upconversion Nanophosphors for Highly Efficient UCL Imaging and pH‐Responsive Drug Delivery , 2015 .

[29]  Jun Lin,et al.  Current Advances in Lanthanide Ion (Ln3+)-Based Upconversion Nanomaterials for Drug Delivery , 2015 .

[30]  Jan C. Hummelen,et al.  Broadband dye-sensitized upconversion of near-infrared light , 2012, Nature Photonics.

[31]  R. Kumar,et al.  Bioconjugated Pluronic Triblock-Copolymer Micelle-Encapsulated Quantum Dots for Targeted Imaging of Cancer: In Vitro and In Vivo Studies , 2012, Theranostics.

[32]  Christopher G. Morgan,et al.  The Active‐Core/Active‐Shell Approach: A Strategy to Enhance the Upconversion Luminescence in Lanthanide‐Doped Nanoparticles , 2009 .

[33]  Xiaogang Liu,et al.  Photonics: Upconversion goes broadband. , 2012, Nature materials.

[34]  H. Dai,et al.  Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Zhen Cheng,et al.  In vitro and in vivo uncaging and bioluminescence imaging by using photocaged upconversion nanoparticles. , 2012, Angewandte Chemie.

[36]  Paras N. Prasad,et al.  (α-NaYbF4:Tm(3+))/CaF2 core/shell nanoparticles with efficient near-infrared to near-infrared upconversion for high-contrast deep tissue bioimaging. , 2012, ACS nano.

[37]  Ling-Dong Sun,et al.  Nd(3+)-sensitized upconversion nanophosphors: efficient in vivo bioimaging probes with minimized heating effect. , 2013, ACS nano.

[38]  Yong Zhang,et al.  Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers , 2012, Proceedings of the National Academy of Sciences.

[39]  C. Brabec,et al.  Rare‐Earth Ion Doped Up‐Conversion Materials for Photovoltaic Applications , 2011, Advanced materials.

[40]  C. G. Morgan,et al.  Upconverting Nanoparticles: The Active‐Core/Active‐Shell Approach: A Strategy to Enhance the Upconversion Luminescence in Lanthanide‐Doped Nanoparticles (Adv. Funct. Mater. 18/2009) , 2009 .

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

[42]  E. Isacoff,et al.  Scanless two-photon excitation of channelrhodopsin-2 , 2010, Nature Methods.

[43]  Paras N. Prasad,et al.  Upconversion: Tunable Near Infrared to Ultraviolet Upconversion Luminescence Enhancement in (α‐NaYF4:Yb,Tm)/CaF2 Core/Shell Nanoparticles for In situ Real‐time Recorded Biocompatible Photoactivation (Small 19/2013) , 2013 .

[44]  R. Bandyopadhyay,et al.  Encapsulation of hydrophobic drugs in Pluronic F127 micelles: effects of drug hydrophobicity, solution temperature, and pH. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[45]  B. Cohen,et al.  Rationally Designed Energy Transfer in Upconverting Nanoparticles , 2015, Advanced materials.