In Vivo Subcutaneous Thermal Video Recording by Supersensitive Infrared Nanothermometers

Some of the old and unrealizable dreams of biomedicine have become possible thanks to the appearance of novel advanced materials such as luminescent nanothermometers, nanoparticles capable of providing a contactless thermal reading through their light emission properties. Luminescent nanothermometers have already been demonstrated to be capable of in vivo subcutaneous punctual thermal reading but their real application as diagnosis tools still requires demonstrating their actual capacity for the acquisition of in vivo, time-resolved subcutaneous thermal images. The transfer from 1D to 2D subcutaneous thermal sensing is blocked in the last years mainly due to the lack of high sensitivity luminescent nanothermometers operating in the infrared biological windows. This work demonstrates how core/shell engineering, in combination with selective rare earth doping, can be used to develop supersensitive infrared luminescent nanothermometers. Erbium, thulium, and ytterbium core–shell LaF3 nanoparticles, operating within the biological windows, provide thermal sensitivities as large as 5% °C−1. This “record” sensitivity has allowed for the final acquisition of subcutaneous thermal videos of a living animal. Subsequent analysis of thermal videos allows for an unequivocal determination of intrinsic properties of subcutaneous tissues, opening the venue to the development of novel thermal imaging-based diagnosis tools.

[1]  T. Grzyb,et al.  Photoluminescent properties of LaF3:Eu3+ and GdF3:Eu3+ nanoparticles prepared by co-precipitation method , 2009 .

[2]  D. Jaque,et al.  Self-monitored photothermal nanoparticles based on core-shell engineering. , 2016, Nanoscale.

[3]  M. A. Kurochkin,et al.  Nd3+ single doped YVO4 nanoparticles for sub-tissue heating and thermal sensing in the second biological window , 2017 .

[4]  S. E. Godoy,et al.  Dynamic infrared imaging for skin cancer screening , 2015 .

[5]  Cila Herman,et al.  The role of dynamic infrared imaging in melanoma diagnosis. , 2013, Expert review of dermatology.

[6]  Elodie Boisselier,et al.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. , 2009, Chemical Society reviews.

[7]  Shuo Diao,et al.  Biological imaging using nanoparticles of small organic molecules with fluorescence emission at wavelengths longer than 1000 nm. , 2013, Angewandte Chemie.

[8]  Robert R. Alfano,et al.  Deep optical imaging of tissue using the second and third near-infrared spectral windows , 2014, Journal of biomedical optics.

[9]  J. G. Solé,et al.  Hybrid Nanostructures for High‐Sensitivity Luminescence Nanothermometry in the Second Biological Window , 2015, Advanced materials.

[10]  A. N. Bashkatov,et al.  Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm , 2005 .

[11]  Renren Deng,et al.  Tuning upconversion through energy migration in core-shell nanoparticles. , 2011, Nature materials.

[12]  Vineet Kumar Rai,et al.  A comparative study of FIR and FL based temperature sensing schemes: an example of Pr3+ , 2007 .

[13]  A. Benayas,et al.  Double rare-earth nanothermometer in aqueous media: opening the third optical transparency window to temperature sensing. , 2017, Nanoscale.

[14]  J. G. Solé,et al.  1.3 μm emitting SrF2:Nd3+ nanoparticles for high contrast in vivo imaging in the second biological window , 2015, Nano Research.

[15]  M. C. Mancini,et al.  Bioimaging: second window for in vivo imaging. , 2009, Nature nanotechnology.

[16]  Dean Ho,et al.  Multimodal Nanodiamond Drug Delivery Carriers for Selective Targeting, Imaging, and Enhanced Chemotherapeutic Efficacy , 2011, Advanced materials.

[17]  Kohei Soga,et al.  Upconverting and NIR emitting rare earth based nanostructures for NIR-bioimaging. , 2013, Nanoscale.

[18]  Daniel Jaque,et al.  LaF3 core/shell nanoparticles for subcutaneous heating and thermal sensing in the second biological-window , 2016 .

[19]  J. G. Solé,et al.  Heating efficiency of multi-walled carbon nanotubes in the first and second biological windows. , 2013, Nanoscale.

[20]  D. Jaque,et al.  In vivo autofluorescence in the biological windows: the role of pigmentation , 2016, Journal of biophotonics.

[21]  Tal Dvir,et al.  Nanoparticles targeting the infarcted heart. , 2011, Nano letters.

[22]  L. Carlos,et al.  Boosting the sensitivity of Nd(3+)-based luminescent nanothermometers. , 2015, Nanoscale.

[23]  R. Anderson,et al.  The optics of human skin. , 1981, The Journal of investigative dermatology.

[24]  B. Wall,et al.  Rare-earth-doped biological composites as in vivo shortwave infrared reporters , 2013, Nature Communications.

[25]  W. Stręk,et al.  Near infrared absorbing near infrared emitting highly-sensitive luminescent nanothermometer based on Nd(3+) to Yb(3+) energy transfer. , 2015, Physical chemistry chemical physics : PCCP.

[26]  A. Benayas,et al.  Infrared‐Emitting QDs for Thermal Therapy with Real‐Time Subcutaneous Temperature Feedback , 2016 .

[27]  Qian Wang,et al.  Structure- and temperature-sensitive photoluminescence in a novel phosphate red phosphor RbZnPO4:Eu(3.). , 2015, Dalton transactions.

[28]  M. Eremets,et al.  Ammonia as a case study for the spontaneous ionization of a simple hydrogen-bonded compound , 2014, Nature Communications.

[29]  Xiaoming Li,et al.  Epitaxial seeded growth of rare-earth nanocrystals with efficient 800 nm near-infrared to 1525 nm short-wavelength infrared downconversion photoluminescence for in vivo bioimaging. , 2014, Angewandte Chemie.

[30]  Muthu Kumara Gnanasammandhan,et al.  Optical imaging-guided cancer therapy with fluorescent nanoparticles , 2010, Journal of The Royal Society Interface.

[31]  D. Jaque,et al.  Unveiling in Vivo Subcutaneous Thermal Dynamics by Infrared Luminescent Nanothermometers. , 2016, Nano letters.

[32]  Guosong Hong,et al.  Multifunctional in vivo vascular imaging using near-infrared II fluorescence , 2012, Nature Medicine.

[33]  H. Dai,et al.  Biological imaging without autofluorescence in the second near-infrared region , 2015, Nano Research.

[34]  D. Jaque,et al.  In Vivo Luminescence Nanothermometry: from Materials to Applications , 2017 .

[35]  S. Jacques Optical properties of biological tissues: a review , 2013, Physics in medicine and biology.

[36]  O. Savchuk,et al.  Luminescence thermometry and imaging in the second biological window at high penetration depth with Nd:KGd(WO4)2 nanoparticles , 2016 .

[37]  Lei Zhou,et al.  Nd3+ Sensitized Up/Down Converting Dual-Mode Nanomaterials for Efficient In-vitro and In-vivo Bioimaging Excited at 800 nm , 2013, Scientific Reports.

[38]  B. Tromberg,et al.  Non-invasive measurements of breast tissue optical properties using frequency-domain photon migration. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[39]  Stephen J. Lomnes,et al.  Tissue-like phantoms for near-infrared fluorescence imaging system assessment and the training of surgeons. , 2006, Journal of biomedical optics.

[40]  Qiangbin Wang,et al.  A novel photoacoustic nanoprobe of ICG@PEG-Ag2S for atherosclerosis targeting and imaging in vivo. , 2016, Nanoscale.

[41]  D. Jaque,et al.  Ag/Ag2S Nanocrystals for High Sensitivity Near‐Infrared Luminescence Nanothermometry , 2017 .

[42]  M. Samoć,et al.  Neodymium(III) doped fluoride nanoparticles as non-contact optical temperature sensors. , 2012, Nanoscale.

[43]  T. T. Vo Doan,et al.  Glue-Free Stacked Luminescent Nanosheets Enable High-Resolution Ratiometric Temperature Mapping in Living Small Animals. , 2016, ACS applied materials & interfaces.

[44]  W. Stręk,et al.  Optimization of highly sensitive YAG:Cr3+,Nd3+ nanocrystal-based luminescent thermometer operating in an optical window of biological tissues. , 2017, Physical chemistry chemical physics : PCCP.

[45]  Hongjie Dai,et al.  Ag2S quantum dot: a bright and biocompatible fluorescent nanoprobe in the second near-infrared window. , 2012, ACS nano.

[46]  P. Couvreur,et al.  Nanoparticles in cancer therapy and diagnosis. , 2002, Advanced drug delivery reviews.

[47]  Omar K. Yaghi,et al.  In vivo fluorescence imaging in the second near-infrared window with long circulating carbon nanotubes capable of ultrahigh tumor uptake. , 2012, Journal of the American Chemical Society.

[48]  D. Jaque,et al.  In Vivo Ischemia Detection by Luminescent Nanothermometers , 2017, Advanced healthcare materials.

[49]  Luís D Carlos,et al.  Thermometry at the nanoscale. , 2015, Nanoscale.

[50]  D. Murata,et al.  Near-infrared long persistent luminescence of Er3+ in garnet for the third bio-imaging window , 2016 .

[51]  François Légaré,et al.  Exploiting the biological windows: current perspectives on fluorescent bioprobes emitting above 1000 nm. , 2016, Nanoscale horizons.

[52]  Ilmo Sildos,et al.  Relation of Crystallinity and Fluorescent Properties of LaF3:Nd3+ Nanoparticles Synthesized with Different Water-Based Techniques , 2017 .

[53]  Xiaoman Zhang,et al.  A core-shell-shell nanoplatform upconverting near-infrared light at 808 nm for luminescence imaging and photodynamic therapy of cancer , 2015, Scientific Reports.

[54]  Wei Feng,et al.  Temperature-feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature , 2016, Nature Communications.

[55]  J. W. Stouwdam,et al.  Near-infrared Emission of Redispersible Er3+, Nd3+, and Ho3+ Doped LaF3 Nanoparticles , 2002 .

[56]  Thomas Thundat,et al.  Pulsed Laser Deposited Dysprosium‐Doped Gadolinium–Vanadate Thin Films for Noncontact, Self‐Referencing Luminescence Thermometry , 2016, Advanced materials.

[57]  M. Dramićanin Sensing temperature via downshifting emissions of lanthanide-doped metal oxides and salts. A review , 2016, Methods and applications in fluorescence.

[58]  K. Soga,et al.  Ratiometric near-infrared fluorescence nanothermometry in the OTN-NIR (NIR II/III) biological window based on rare-earth doped β-NaYF4 nanoparticles. , 2017, Journal of materials chemistry. B.

[59]  H. Hofsäss,et al.  Demonstration of Temperature Dependent Energy Migration in Dual-Mode YVO4: Ho3+/Yb3+ Nanocrystals for Low Temperature Thermometry , 2016, Scientific Reports.