Patricia Haro-González

Fluorescent nanothermometers for intracellular thermal sensing

The importance of high-resolution intracellular thermal sensing and imaging in the field of modern biomedicine has boosted the development of novel nanosized fluorescent systems (fluorescent nanothermometers) as the next generation of probes for intracellular thermal sensing and imaging. This thermal mapping requires fluorescent nanothermometers with good biocompatibility and high thermal sensitivity in order to obtain submicrometric and subdegree spatial and thermal resolutions, respectively. This review describes the different nanosized systems used up to now for intracellular thermal sensing and imaging. We also include the later advances in molecular systems based on fluorescent proteins for thermal mapping. A critical overview of the state of the art and the future perspective is also included.

Heating efficiency of multi-walled carbon nanotubes in the first and second biological windows.

Quantum dot based-thermometry, in combination with double beam confocal microscopy and infrared thermal imaging, has been used to investigate the heating efficiency of multi-walled carbon nanotubes (MWCNTs) under optical excitation within the first (808 nm) and second (1090 nm) biological windows as well as in the spectral region separating them (980 nm). It has been found that for the three excitation wavelengths the heating efficiency of MWCNTs (10 nm in diameter and 1.5 μm in length) is close to 50%. Despite this flat heating efficiency, we have found that the excitation wavelength is, indeed, critical during in vivo experiments due to the spectral dependence of both tissue absorption and scattering coefficients. It has been concluded that efficiency and selectivity of in vivo photothermal treatments based on MWCNTs are simultaneously optimized when laser irradiation lies within the first or second biological window.

Fluorescent nanothermometers provide controlled plasmonic-mediated intracellular hyperthermia

AIMnThis article demonstrates how controlled hyperthermia at the cellular level can be achieved.nnnMATERIALS & METHODSnThe method is based on the simultaneous intracellular incorporation of fluorescence nanothermometers (CdSe quantum dots) and metallic nanoheaters (gold nanorods).nnnRESULTSnReal-time spectral analysis of the quantum dot emission provides a detailed feedback about the intracellular thermal loading caused by gold nanorods excited at the plasmon frequency. Based on this approach, thermal dosimetry is assessed in such a way that the infrared laser (heating) power required to achieve catastrophic intracellular temperature increments in cancer cells is identified.nnnCONCLUSIONSnThis pure optical method emerges as a new and promising guide for the development of infrared hyperthermia therapies with minimal invasiveness.

Quantum Dot Thermometry Evaluation of Geometry Dependent Heating Efficiency in Gold Nanoparticles

Quantum dot based thermometry, in combination with double beam confocal microscopy, was used to investigate the absorption/heating efficiency of gold nanoparticles with different morphologies (nanorods, nanocages, nanoshells, and nanostars), all of them with an intense localized surface plasmon resonance within the first biological window, at around 808 nm. The heating efficiency was found to be strongly dependent on the geometry of the nanostructure, with the largest values found for gold nanorods and long-edge gold nanostars, both of them with heating efficiencies close to 100%. Gold nanorods and nanocages were found to have the largest absorption cross section per unit mass among all the studied geometries, emerging as optimum photothermal agents with minimum metal loading for biosystems.

Quantum Dot‐Based Thermal Spectroscopy and Imaging of Optically Trapped Microspheres and Single Cells

Laser-induced thermal effects in optically trapped microspheres and single cells are investigated by quantum dot luminescence thermometry. Thermal spectroscopy has revealed a non-localized temperature distribution around the trap that extends over tens of micrometers, in agreement with previous theoretical models besides identifying water absorption as the most important heating source. The experimental results of thermal loading at a variety of wavelengths reveal that an optimum trapping wavelength exists for biological applications close to 820 nm. This is corroborated by a simultaneous analysis of the spectral dependence of cellular heating and damage in human lymphocytes during optical trapping. This quantum dot luminescence thermometry demonstrates that optical trapping with 820 nm laser radiation produces minimum intracellular heating, well below the cytotoxic level (43 °C), thus, avoiding cell damage.

Thermal Scanning at the Cellular Level by an Optically Trapped Upconverting Fluorescent Particle.

3D optical manipulation of a thermal-sensing upconverting particle allows for the determination of the extension of the thermal gradient created in the surroundings of a plasmonic-mediated photothermal-treated HeLa cancer cell.

Optical trapping of NaYF4:Er3+,Yb3+ upconverting fluorescent nanoparticles

We report on the first experimental observation of stable optical trapping of dielectric NaYF4:Er(3+),Yb(3+) upconverting fluorescent nanoparticles (~26 nm in diameter) using a continuous wave 980 nm single-beam laser. The laser serves both to optically trap and to excite visible luminescence from the nanoparticles. Sequential loading of individual nanoparticles into the trap is observed from the analysis of the emitted luminescence. We demonstrate that the trapping strength and the number of individual nanoparticles trapped are dictated by both the laser power and nanoparticle density. The possible contribution of thermal effects has been investigated by performing trapping experiment in both heavy water and into distilled water. For the case of heavy water, thermal gradients are negligible and optical forces dominate the trap loading behaviour. The results provide a promising path towards real three dimensional manipulation of single NaYF4:Er(3+),Yb(3+) nanoparticles for precise fluorescence sensing in biophotonics experiments.

Absorption efficiency of gold nanorods determined by quantum dot fluorescence thermometry

In this work quantum dot fluorescence thermometry, in combination with double-beam confocal microscopy, has been applied to determine the thermal loading of gold nanorods when subjected to an optical excitation at the longitudinal surface plasmon resonance. The absorbing/heating efficiency of low (≈3) aspect ratio gold nanorods has been experimentally determined to be close to 100%, in excellent agreement with theoretical simulations of the extinction, absorption, and scattering spectra based on the discrete dipole approximation.

Assessing Single Upconverting Nanoparticle Luminescence by Optical Tweezers.

We report on stable, long-term immobilization and localization of a single colloidal Er(3+)/Yb(3+) codoped upconverting fluorescent nanoparticle (UCNP) by optical trapping with a single infrared laser beam. Contrary to expectations, the single UCNP emission differs from that generated by an assembly of UCNPs. The experimental data reveal that the differences can be explained in terms of modulations caused by radiation-trapping, a phenomenon not considered before but that this work reveals to be of great relevance.

Evaluation of rare earth doped silica sub-micrometric spheres as optically controlled temperature sensors

We report on the evaluation of rare earth (Er3+, Eu3+, and Tb3+ ions) SiO2 sub-micrometric spheres as potential optically controllable temperature sensors. Details about fabrication, optical manipulation and spectroscopic characterization of the sub-micrometric spheres are presented. The fluorescence properties of the micros-spheres in the biological range (25–60u2009°C) have been systematically investigated. From this systematic study, the thermal resolution potentially achieved in each case has been determined and compared to previous works.