Targeted complexes based on upconversion nanoparticles for imaging in the first and second optical tissue transparency window

Background: Upconverting nanoparticles (UCNPs) represent a unique class of nanomaterials, able to convert infrared excitation light into long lifetime visible and infrared photoluminescence, within the “optical transparency window” of biological tissues. This makes UCNPs an attractive contrast agent for background-free bioimaging. However, assynthesized UCNPs are hydrophobic and need additional surface coating for stability in water-based solutions and further functionalization. Polyethylenimine (PEI), a polycationic amphiphilic polymer, is a well-known transfection agent for gene delivery and a popular material for UCNPs surface hydrophilization. Combining the functional properties of UCNPs and PEI is extremely useful for precise visualization of genetic manipulations and intracellular drug delivery. At the same time, PEI is toxic to cells, while the photoluminescent properties of UCNPs are very sensitive to surface chemistry and environment. Then, creation of hydrophilic, biocompatible and simultaneously bright UCNPs, modified by PEI (UCNP-PEI), is a challenging task. Objectives: To analyze the effects of multilayer shielding coatings on cytotoxicity, cellular uptake and photoluminescent properties of UCNP-PEI. Methods and results: UCNP-PEI were modified with additional two or three layers of various polymers and characterized by size, surface charge and photophysical properties. HaCaT keratinocytes were exposed to the particles for 24 or 120 h to study the cytotoxicity and cellular uptake. The results show that onion-like coatings of UCNP-PEI simultaneously decrease cytotoxicity and relative luminescence of the particles, depending on structure and method of formation of multilayer coating. Conclusions: Rational design of UCNP-PEI using extra coatings layers can help to keep acceptable levels of biocompatibility and photoluminescence intensity.

The use of nanoparticles in medical applications has been gaining momentum as antibody-conjugated nanoparticles are becoming more and more feasible as a means of targeted delivery of various therapies. Irradiating nanoparticles with light of strongly-absorbed wavelengths allows them to act as heat generation sites. Two therapies utilize these nanoparticle heat sources to kill the target cells: nanophotohyperthermia, which heats the particles just enough to disrupt cell function and trigger cell death; and nanophotothermolysis, which heats the particles to such extremes as to destroy the cell membrane. The use of optical wavelengths in the range of 750-1100 nm has been to capitalize on the "optical transparency window" of biotissues between the absorption peaks of hemoglobin in the visible end and water in the near-IR. However, further research has shown that a plasmon resonance can greatly affect the absorption characteristics of nanoparticles at the plasmon resonant frequency, allowing for increased absorption characteristics at desirable wavelengths. Thus, other transparency windows may find use in a similar manner, such as nanoparticle heating by RF waves. This paper presents the modeling of 3D thermal fields around nanoparticle absorbers in bone tissue for various frequencies. A comparison of the heating effectiveness across multiple wavelengths is discussed for application to nanophotothermolysis and nanophotohyperthermia treatments in or near biological hard tissue.

A material exhibiting a wide-band optical transparent window (OTW) with negligible transmittance fluctuation is highly desired in various applications, but the conventional approach of stacking multiple transmission-resonant metasurfaces creates undesired amplitude fluctuations within the OTW. In this article, we first establish a coupled-mode theory to understand the inherent physics governing the transmission properties in such systems, based on which we then propose a criterion that can help researchers design structures exhibiting wide-band OTWs with diminished transmittance fluctuations. Compared to a brute-force optimization method, our approach is much faster and physically intuitive. As an illustration of our theory, we design a four-layer structure (with a total thickness of 36 mm) through solving the proposed criterion, and experimentally demonstrate that it exhibits a flat OTW within the 3.7–5 GHz range, with transmittance fluctuations smaller than 10 percent. Our findings can stimulate the design of artificial structures exhibiting the desired shapes of transmission windows fitting applications in different frequency regimes.

First-principles calculations for understanding high conductivity and optical transparency in In xCd 1− xO films

Growth of optically transparent single crystals of thiourea succinic acid (TUSA) was grown successfully from aqueous solution by slow evaporation technique. The crystal structure was elucidated using the single crystal XRD. The various functional groups and the modes of vibrations were identified by FT-IR spectroscopic analysis. The optical absorption studies indicate that the optical transparency window is quite wide making its suitable for NLO applications. Thermal stability of the crown crystal carried out by TGA-DTA analysis.

The slow evaporation solution growth method was employed to successfully grow single crystals of oxalic acid ammonium dichromate (OAAD). x‐Ray diffraction (XRD) examination was utilized to verify the grown samples' structural integrity and crystallinity. Thorough spectroscopic analyses, such as FTIR spectroscopy and UV–vis–NIR absorption, demonstrated the presence of functional groups related to nonlinear optical (NLO) activity as well as an optical transparency window. To evaluate the material's suitability for photonic applications, linear optical metrics, including the absorption coefficient, refractive index, and optical band gap, were computed. The Kurtz–Perry powder approach was implemented to assess nonlinear optical behavior, and the results validated the efficiency of second harmonic generation (SHG), indicating a high NLO response. The effective relative second harmonic generation efficiency of OAAD is 0.93 times greater than that of the reference material KDP. The broad band gap, demonstrable SHG efficiency, and good optical transparency of OAAD crystals highlight their potential as prospective candidates for advanced photonic and optoelectronic devices.

ABSTRACTThis contribution reports the in situ growth of transparent, conducting GaxIn2-xO3 and ZnkIn2Ok+3 films by MOCVD (metal-organic chemical vapor deposition) techniques using In(dpm)3, Ga(dpm)3, and Zn(dpm)2 (dpm = dipivaloylmethanate) as volatile precursors. In the former series, film microstructure in the x = 0.4 – 1.0 range is predominantly cubic with 25° C electrical conductivities as high as 1300 S/cm (n-type; carrier density = 1.2 × 1020 cm−3, mobility = 68 cm2/Vs) and optical transparency in the visible region greater than that of ITO. In the latter series, films in the composition range K = 0.16 – 3.60 were studied; the microstructural systematics are rather complex. Electrical conductivities (25° C) as high as 1000 S/cm (n-type; carrier density = 3.7 × 1020 cm−3, mobility = 18.6 cm2/Vs) for K = 0.66 were measured. The optical transparency window is significantly broader than that of ITO.

Transparent metallic oxides are pivotal materials in information technology, photovoltaics, or even in architecture. They display the rare combination of metallicity and transparency in the visible range because of weak interband photon absorption and weak screening of free carriers to impinging light. However, the workhorse of current technology, indium tin oxide (ITO), is facing severe limitations and alternative approaches are needed. AMO3 perovskites, M being a nd1 transition metal, and A an alkaline earth, have a genuine metallic character and, in contrast to conventional metals, the electron–electron correlations within the nd1 band enhance the carriers effective mass (m*) and bring the transparency window limit (marked by the plasma frequency, ωp*) down to the infrared. Here, it is shown that epitaxial strain and carrier concentration allow fine tuning of optical properties (ωp*) of SrVO3 films by modulating m* due to strain‐induced selective symmetry breaking of 3d‐t2g(xy, yz, xz) orbitals. Interestingly, the DC electrical properties can be varied by a large extent depending on growth conditions whereas the optical transparency window in the visible is basically preserved. These observations suggest that the harsh conditions required to grow optimal SrVO3 films may not be a bottleneck for their future application.

Application of NIR (near-infrared) emitting transition metal complexes in biomedicine is a rapidly developing area of research. Emission of this class of compounds in the "optical transparency windows" of biological tissues and the intrinsic sensitivity of their phosphorescence to oxygen resulted in the preparation of several commercial oxygen sensors capable of deep (up to whole-body) and quantitative mapping of oxygen gradients suitable for in vivo experimental studies. In addition to this achievement, the last decade has also witnessed the increased growth of successful alternative applications of NIR phosphors that include (i) site-specific in vitro and in vivo visualization of sophisticated biological models ranging from 3D cell cultures to intact animals; (ii) sensing of various biologically relevant analytes, such as pH, reactive oxygen and nitrogen species, RedOx agents, etc.; (iii) and several therapeutic applications such as photodynamic (PDT), photothermal (PTT), and photoactivated cancer (PACT) therapies as well as their combinations with other therapeutic and imaging modalities to yield new variants of combined therapies and theranostics. Nevertheless, emerging applications of these compounds in experimental biomedicine and their implementation as therapeutic agents practically applicable in PDT, PTT, and PACT face challenges related to a critically important improvement of their photophysical and physico-chemical characteristics. This review outlines the current state of the art and achievements of the last decade and stresses the most promising trends, major development prospects, and challenges in the design of NIR phosphors suitable for biomedical applications.

Nanophotonics is an emerging science dealing with the interaction of light and matter on a nanometer scale and holds promise to produce new generation nanophosphors with highly efficient frequency conversion of infrared (IR) light. Scientists can control the excitation dynamics by using nanochemistry to produce hierarchically built nanostructures and tailor their interfaces. These nanophosphors can either perform frequency up-conversion from IR to visible or ultraviolet (UV) or down-conversion, which results in the IR light being further red shifted. Nanophotonics and nanochemistry open up numerous opportunities for these photon converters, including in high contrast bioimaging, photodynamic therapy, drug release and gene delivery, nanothermometry, and solar cells. Applications of these nanophosphors in these directions derive from three main stimuli. Light excitation and emission within the near-infrared (NIR) "optical transparency window" of tissues is ideal for high contrast in vitro and in vivo imaging. This is due to low natural florescence, reduced scattering background, and deep penetration in tissues. Secondly, the naked eye is highly sensitive in the visible range, but it has no response to IR light. Therefore, many scientists have interest in the frequency up-conversion of IR wavelengths for security and display applications. Lastly, frequency up-conversion can convert IR photons to higher energy photons, which can then readily be absorbed by solar materials. Current solar devices do not use abundant IR light that comprises almost half of solar energy. In this Account, we present our recent work on nanophotonic control of frequency up- and down-conversion in fluoride nanophosphors, and their biophotonic and nanophotonic applications. Through nanoscopic control of phonon dynamics, electronic energy transfer, local crystal field, and surface-induced non-radiative processes, we were able to produce new generation nanophosphors with highly efficient frequency conversion of IR light. We show that nanochemistry plays a vital role in the design and interface engineering of nanophosphors, providing pathways to expand their range of applications. High contrast in vitro and in vivo NIR-to-NIR up- and down-conversion bioimaging were successfully demonstrated by our group, evoking wide interests along this line. We introduced trivalent gadolinium ions into the lattice of the nanophosphors or into the shell layer of nanophosphors in a core/shell configuration to produce novel nanophosphors for multimodal (MRI and optical) imaging. We also demonstrate the security and display applications using photopatternable NIR-to-NIR and NIR-to-visible frequency up-conversion nanophosphors with appropriately engineered surface chemistry. In addition, we present preliminary results on dye-sensitized solar cells using up-conversion in fluoride lattice-based nanophosphors for IR photon harvesting.

Optical coherence tomography (OCT) is an imaging technique affording noninvasive optical biopsies. Like for other imaging techniques, the use of dedicated contrast agents helps better discerning biological features of interest during the clinical practice. Although bright OCT contrast agents have been developed, no dark counterpart has been proposed yet. Herein, plasmonic copper sulfide nanoparticles as the first OCT dark contrast agents working in the second optical transparency window are reported. These nanoparticles virtually possess no light scattering capabilities at the OCT working wavelength (≈1300 nm); thus, they exclusively absorb the probing light, which in turn results in dark contrast. The small size of the nanoparticles and the absence of apparent cytotoxicity support the amenability of this system to biomedical applications. Importantly, in the pursuit of systems apt to yield OCT dark contrast, a library of copper sulfide nanoparticles featuring plasmonic resonances spanning the three optical transparency windows is prepared, thus highlighting the versatility and potential of these systems in light-controlled biomedical applications.

Owing to the alluring possibility of contactless temperature probing with microscopic spatial resolution, photoluminescence nanothermometry at the nanoscale is rapidly advancing towards its successful application in biomedical sciences. The emergence of near-infrared nanothermometers has paved the way for temperature sensing at the deep tissue level. However, water dispersibility, adequate size at the nanoscale, and the capability to efficiently operate in the second and third biological optical transparency windows are the requirements that still have to be fulfilled in a single nanoprobe. In this work, these requirements are addressed by rare-earth doped nanoparticles with core/shell-architecture, dispersed in water, whose excitation and emission wavelengths conveniently fall within the biological optical transparency windows. Under heating-free 800 nm excitation, double nanothermometry is realized either with Ho3+-Nd3+ (1.18-1.34 μm) or Er3+-Nd3+ (1.55-1.34 μm) NIR emission band ratios, both displaying equal thermal sensitivities around 1.1% °C-1. It is further demonstrated that, along with the interionic energy transfer processes, the thermometric properties of these nanoparticles are also governed by the temperature dependent energy transfer to the surrounding solvent (water) molecules. Overall, this work presents a novel water dispersible double ratiometric nanothermometer operating in the second and third biological optical transparency windows. The temperature dependent particle-solvent interaction is also presented, which is critical for e.g. future in vivo applications.

Upconversion in rare-earth ions is a sequential multiphoton process that efficiently converts two or more low-energy photons, which are generally near infrared (NIR) light, to produce anti-Stokes emission of a higher energy photon (e.g., NIR, visible, ultraviolet) using continuous-wave (cw) diode laser excitation. Here, we show the engineering of novel, efficient, and biocompatible NIR_in-to-NIR_out upconversion nanoparticles for biomedical imaging with both excitation and emission being within the "optical transparency window" of tissues. The small animal whole-body imaging with exceptional contrast (signal-to-noise ratio of 310) was shown using BALB/c mice intravenously injected with aqueously dispersed nanoparticles. An imaging depth as deep as 3.2-cm was successfully demonstrated using thick animal tissue (pork) under cw laser excitation at 980 nm.

Fluorescence imaging (FI) employing near-infrared (NIR) light within the range of ~750-1350 nm enables biomedical imaging several millimeters beneath the tissue surface. More recent investigations into the short-wave IR (SWIR) transparency windows between ~1550-1870 and 2100-2300 nm highlight their superior capabilities. This research presents a comparison of IR-FI of PbS quantum dots, emitting at 990, 1310, and 1580 nm, through the mouse scalp skin, skull, and brain. The SWIR fluorescence is the most effectively transmitted signal, showing particularly significant enhancement when passing through the skull, which causes high light scattering. For the analysis of the imaging results and light propagation through the organs, their spectra of attenuation, absorption, and scattering coefficients are measured. In view of biomedical imaging, attenuation due to light scattering is a more destructive factor. Hence, the spatial resolution and imaging contrast can be improved by operating in SWIR due to decreased light scattering.

Plasmon-induced transparency and Fano resonances in metal-insulator-metal nanorod dimers: A numerical analysis