Biological Window Research Articles

Rationally Designed Long-Wavelength Absorbing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy.

The utilization of photodynamic therapy (PDT) for the treatment of various types of cancer has gained increasing attention over the last decades. Despite the clinical success of approved photosensitizers (PSs), their application is sometimes limited due to poor water solubility, aggregation, photodegradation, and slow clearance from the body. To overcome these drawbacks, research efforts are devoted toward the development of metal complexes and especially Ru(II) polypyridine complexes based on their attractive photophysical and biological properties. Despite the recent research developments, the vast majority of complexes utilize blue or UV-A light to obtain a PDT effect, limiting the penetration depth inside tissues and, therefore, the possibility to treat deep-seated or large tumors. To circumvent these drawbacks, we present the first example of a DFT guided search for efficient PDT PSs with a substantial spectral red shift toward the biological spectral window. Thanks to this design, we have unveiled a Ru(II) polypyridine complex that causes phototoxicity in the very low micromolar to nanomolar range at clinically relevant 595 nm, in monolayer cells as well as in 3D multicellular tumor spheroids.

Eu3+−doped titanium oxide nanoparticles for optical thermometry in the first biological window

Lanthanide-based optical nanothermometers, operating in the physiological temperature range (288–323 K), with excitation and emission in the first biological transparent window have special interest for biological applications. In this context, trivalent europium doped titanium oxide (Eu3+:TiO2) nanoparticles were prepared via a sol-gel method and their spectroscopic properties were studied. In order to assess their potential for temperature sensing, excitation and luminescence spectroscopies were performed. We observed that the intensities of the excitation bands for the 7F0→5D0 (576 nm) and 7F2→5D0 (610 nm) transitions, monitoring the 5D0→7F4 (700 nm) transition have a strong dependence on temperature. This dependence, which is explained in terms of a thermal coupling between the Eu3+:7FJ levels, was used for the construction of an optical nanothermometer. Relative sensitivity values between 1.78 and 1.41% K−1, when the temperature of the material increases from 288 to 323 K, were obtained. We show that the nanothermometer calibration can be obtained by a single luminescence room temperature measurement. Our results indicate the potential application of Eu3+:TiO2 nanoparticles for temperature sensing in the first biological window and physiological temperature range.

Doping of resonant silicon nanodisks for efficient optical heating in the near-infrared range

All-dielectric nanophotonics attracted high interest during last years in the field of thermal applications and optical heating mainly due to the ability of electromagnetic field localization inside the nanostructures due to different resonant modes excitation. However, most conventional dielectrics and semiconductors (e.g. silicon, germanium etc.) are transparent in the near-IR, and, thus, optical heating in this region becomes a challenging task. In this work, we reveal that carrier doping can significantly increase optical heating of a resonant silicon nanodisk, without changing its optical properties dramatically. In addition, semiconductor nanostructures support high-Q thermally responsive Raman signal, which can be used as the temperature sensor at the nanoscale. We believe, that such approach might be very effective for numbers of applications, including bio-medical ones, by working in the’biological tissue window’.

Adolescent Use of Hair Dyes, Chemical Straighteners and Perms in Relation to Breast Cancer Risk in the Sister Study

Abstract Hair products may contain hormonally active and carcinogenic compounds. We evaluated the risk of breast cancer associated with adolescent use of hair dyes, chemical straighteners and perms in a large prospective U.S. cohort. Methods: Sister Study participants (n = 47,833) were ages 35–74 years and had a sister who had been diagnosed with breast cancer at the time of enrollment (2003–2009). Enrollment questionnaires obtained information on demographics and lifestyle factors as well as frequency of use of hair dyes, chemical straighteners, and perms at ages 10–13 years. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between adolescent hair product use and breast cancer risk (invasive cancer and ductal carcinoma in situ). We considered whether associations varied by invasiveness, estrogen receptor (ER) status of the tumor, menopause status and race. Results: Over an average of 8.3 years of follow-up, 2,829 cases were diagnosed. Hair dye use at ages 10–13 years was uncommon and not associated with breast cancer risk (e.g. permanent hair dye, <3%; HR = 0.96, 95% CI: 0.76–1.22). Use of perms (34% non-Hispanic white vs. 8% black women) and straighteners (10% non-Hispanic white vs 75% black women) at ages 10–13 years varied by race. An elevated HR for breast cancer was observed for frequent use of chemical straighteners (HR = 1.27, 95% CI: 0.98–1.65). Though based on small numbers, this association was most pronounced for ER- invasive (HR = 2.04, 95% CI: 0.98–4.24) and premenopausal breast cancer (HR = 2.18, 95% CI 1.27–3.74). Frequent use of perms was also associated with a higher risk of invasive breast cancer and ER- tumors (HR = 1.25, 95% CI: 1.00–1.57 and HR = 1.69, 95%CI: 0.96–2.98, respectively). Although product use varied by race, associations with breast cancer did not. Conclusions: Frequent use of chemical straighteners or perms during the ages of 10–13 years was associated with a higher risk of breast cancer. These results suggest that exposure to the chemicals in these hair products, especially during adolescence which may be an important biological window of susceptibility, may play a role in breast carcinogenesis.

Ultra-sensitive optical nano-thermometer LaPO4: Yb3+/Nd3+ based on thermo-enhanced NIR-to-NIR emissions

Accurate deep-tissue thermometry integrated with bio-imaging and self-heating functions is urgently desired for effective photo-thermal therapy (PTT) with minimized collateral damages. Herein, urchin-like LaPO4: Yb3+/Nd3+ nano-thermometers working in the biological window region were developed with ultra-high sensitivity and sub-degree resolution. Unique thermal enhancement of near-infrared (NIR) emissions (4F3/2 → 4I9/2) over 1000 times was detected, which was systematically investigated based on phonon-assisted energy transfer process. Irradiated by 980 nm laser, the self-heating effects of urchin-like samples were analyzed, while NIR thermal sensing behaviors were evaluated using ladder-like 4F7/2-4F5/2-4F3/2 states as thermal coupled levels (TCLs). The penetration depth of NIR emissions was determined through spectral measurement at varied tissue thickness, and ex vivo experiments were rationally designed to assess the self-heating and thermal reading features of samples in deep-tissues. These findings reveal the great superiority of the present thermo-enhanced NIR-to-NIR nanoprobes for bio-imaging and thermometry in deep-tissues, which opens a promising pathway for self-monitored PTT.

Self-Assembled Monolayers of Copper Sulfide Nanoparticles on Glass as Antibacterial Coatings.

We developed an easy and reproducible synthetic method to graft a monolayer of copper sulfide nanoparticles (CuS NP) on glass and exploited their particular antibacterial features. Samples were fully characterized showing a good stability, a neat photo-thermal effect when irradiated in the Near InfraRed (NIR) region (in the so called “biological window”), and the ability to release controlled quantities of copper in water. The desired antibacterial activity is thus based on two different mechanisms: (i) slow and sustained copper release from CuS NP-glass samples, (ii) local temperature increase caused by a photo-thermal effect under NIR laser irradiation of CuS NP–glass samples. This behavior allows promising in vivo applications to be foreseen, ensuring a “static” antibacterial protection tailored to fight bacterial adhesion in the critical timescale of possible infection and biofilm formation. This can be reinforced, when needed, by a photo-thermal action switchable on demand by an NIR light.

Room-Temperature Defect Qubits in Ultrasmall Nanocrystals.

There is an urgent quest for room-temperature qubits in nanometer-sized, ultrasmall nanocrystals for quantum biosensing, hyperpolarization of biomolecules, and quantum information processing. Thus far, the preparation of such qubits at the nanoscale has remained futile. Here, we present a synthesis method that avoids any interaction of the solid with high-energy particles and uses self-propagated high-temperature synthesis with a subsequent electrochemical method, the no-photon exciton generation chemistry to produce room-temperature qubits in ultrasmall nanocrystals of sizes down to 3 nm with high yield. We first create the host silicon carbide (SiC) crystallites by high-temperature synthesis and then apply wet chemical etching, which results in ultrasmall SiC nanocrystals and facilitates the creation of thermally stable defect qubits in the material. We demonstrate room-temperature optically detected magnetic resonance signal of divacancy qubits with 3.5% contrast from these nanoparticles with emission wavelengths falling in the second biological window (1000–1380 nm). These results constitute the formation of nonperturbative bioagents for quantum sensing and efficient hyperpolarization.

Photoacoustic Imaging: An IR820 Dye–Protein Complex for Second Near‐Infrared Window and Photoacoustic Imaging (Advanced Optical Materials 4/2020)

After mixing a sulfonated NIR-I organic dye (IR820) with human serum albumin (HAS), fluorescence in the biological NIR-II window of the IR820–HSA organic complex increases dramatically, as shown by Yaming Li, Zhen Cheng and co-workers in article number 1901471. In vivo NIR-II imaging with IR820–HSA can noninvasively and dynamically be used to visualize and monitor the physiological and pathological conditions of the vascular system, lymphatic drainage system, and tumor-bearing mice, as well as allow image-guided tumor resection.

Recent Progress in NIR-II Contrast Agent for Biological Imaging.

Fluorescence imaging technology has gradually become a new and promising tool for in vivo visualization detection. Because it can provide real-time sub-cellular resolution imaging results, it can be widely used in the field of biological detection and medical detection and treatment. However, due to the limited imaging depth (1–2 mm) and self-fluorescence background of tissue emitted in the visible region (400–700 nm), it fails to reveal biological complexity in deep tissues. The traditional near infrared wavelength (NIR-I, 650–950 nm) is considered as the first biological window, because it reduces the NIR absorption and scattering from blood and water in organisms. NIR fluorescence bioimaging's penetration is larger than that of visible light. In fact, NIR-I fluorescence bioimaging is still interfered by tissue autofluorescence (background noise), and the existence of photon scattering, which limits the depth of tissue penetration. Recent experimental and simulation results show that the signal-to-noise ratio (SNR) of bioimaging can be significantly improved at the second region near infrared (NIR-II, 1,000–1,700 nm), also known as the second biological window. NIR-II bioimaging is able to explore deep-tissues information in the range of centimeter, and to obtain micron-level resolution at the millimeter depth, which surpass the performance of NIR-I fluorescence imaging. The key of fluorescence bioimaging is to achieve highly selective imaging thanks to the functional/targeting contrast agent (probe). However, the progress of NIR-II probes is very limited. To date, there are a few reports about NIR-II fluorescence probes, such as carbon nanotubes, Ag2S quantum dots, and organic small molecular dyes. In this paper, we surveyed the development of NIR-II imaging contrast agents and their application in cancer imaging, medical detection, vascular bioimaging, and cancer diagnosis. In addition, the hotspots and challenges of NIR-II bioimaging are discussed. It is expected that our findings will lay a foundation for further theoretical research and practical application of NIR-II bioimaging, as well as the inspiration of new ideas in this field.

Thermometric analysis of the near-infrared emission of Nd3+ in Y2SiO5 ceramic powder prepared by combustion synthesis

Nd3+:Y2SiO5 crystalline ceramic powder prepared by combustion synthesis exhibited down-conversion fluorescence when the sample was exposed to CW laser radiation at 532 nm. Three emission bands centered at 879.36 nm, 804.86 nm and 753.21 nm, corresponding to transitions (4F7/2,4S3/2) → 4I9/2, (4F5/2,2H9/2) → 4I9/2 and 4F3/2 → 4I9/2, were observed. A noticeable change on the relative intensities of the transitions in the temperature range 298–673 K occured due to thermal coupling among the excited electronic states. By means of the fluorescence intensity ratio (FIR) technique, we obtained a maximum absolute sensitivity of 2.5 × 10−3 K−1 at 650 K and a relative sensitivity of 2.11% K−1 at 300 K for this material. The Judd-Ofelt standard intensity parameters ratio Ω4/Ω6, a spectroscopy quality factor for laser applications, was estimated from the FIR thermometry data and a value of 1.75 was obtained. The potential use of this material in thermal sensing at the first biological window (700–950 nm) and in lasing applications is discussed.

Plasmonic Nanoassemblies: Tentacles Beat Satellites for Boosting Broadband NIR Plasmon Coupling Providing a Novel Candidate for SERS and Photothermal Therapy.

Optical theranostic applications demand near-infrared (NIR) localized surface plasmon resonance (LSPR) and maximized electric field at nanosurfaces and nanojunctions, aiding diagnosis via Raman or optoacoustic imaging, and photothermal-based therapies. To this end, multiple permutations and combinations of plasmonic nanostructures and molecular "glues" or linkers are employed to obtain nanoassemblies, such as nanobranches and core-satellite morphologies. An advanced nanoassembly morphology comprising multiple linear tentacles anchored onto a spherical core is reported here. Importantly, this core-multi-tentacle-nanoassembly (CMT) benefits from numerous plasmonic interactions between multiple 5 nm gold nanoparticles (NPs) forming each tentacle as well as tentacle to core (15 nm) coupling. This results in an intense LSPR across the "biological optical window" of 650-1100 nm. It is shown that the combined interactions are responsible for the broadband LSPR and the intense electric field, otherwise not achievable with core-satellite morphologies. Further the sub 80 nm CMTs boosted NIR-surface-enhanced Raman scattering (SERS), with detection of SERS labels at 47 × 10-9 m, as well as lower toxicity to noncancerous cell lines (human fibroblast Wi38) than observed for cancerous cell lines (human breast cancer MCF7), presents itself as an attractive candidate for use as biomedical theranostics agents.

LiAl5O8:Fe3+ and LiAl5O8:Fe3+, Nd3+ as a New Luminescent Nanothermometer Operating in 1st Biological Optical Window.

New types of contactless luminescence nanothermometers, namely, LiAl5O8:Fe3+ and LiAl5O8:Fe3+, Nd3+ are presented for the first time, revealing the potential for applications in biological systems. The temperature-sensing capability of the nanocrystals was analyzed in wide range of temperature (−150 to 300 °C). The emission intensity of the Fe3+ ions is affected by the change in temperature, which induces quenching of the 4T1 (4G) → 6A1 (6S) Fe3+ transition situated in the 1st biological window. The highest relative sensitivity in the temperature range (0 to 50 °C) was found to be 0.82% °C (at 26 °C) for LiAl5O8: 0.05% Fe3+ nanoparticles that are characterized by long luminescent lifetime of 5.64 ms. In the range of low and high temperatures the Smax was calculated for LiAl5O8:0.5% Fe3+ to be 0.92% °C at −100 °C and for LiAl5O8:0.01% Fe3+ to be 0.79% °C at 150 °C. The cytotoxicity assessment carried out on the LiAl5O8:Fe3+ nanocrystals, demonstrated that they are biocompatible and may be utilized for in vivo temperature sensing. The ratiometric luminescent nanothermometer, LiAl5O8:Fe3+, Nd3+, which was used as a reference, possesses an Smax = 0.56%/°C at −80 °C, upon separate excitation of Fe3+ and Nd3+ ions using 266 nm and 808 nm light, respectively.

Discovery of near-infrared persistent phosphorescence and Stokes luminescence in Cr3+ and Nd3+ doped GdY2Al3Ga2O12 dual mode phosphors

The near-infrared (NIR) luminescence materials have attracted great attention on account of their potential applications in optical imaging field. In this paper, a series of Cr3+ and Nd3+ doped GdY2Al3Ga2O12 phosphors with luminescence in the biological windows were synthesized using a solid-state reaction method. The crystal field parameters, concentration dependent photoluminescence and persistent luminescence properties of Cr3+ were discussed in detail. Nd3+ ions exhibit perfect NIR to NIR Stokes luminescence in the host. The influence of Nd3+ doping concentration was studied by emission spectra and decay curves. Taking the advantages of both Cr3+ and Nd3+, dual mode phosphors with NIR persistent luminescence and NIR to NIR Stokes luminescence were designed and achieved. Based on the energy transfer process, persistent luminescence and thermo-luminescence curves, the luminescence mechanism was proposed.

Bimodal Nd-Doped LuVO4 Nanoprobes Functionalized with Polyacrilic Acid for X-Ray Computed Tomography and NIR Luminescent Imaging.

Uniform Nd3+-doped LuVO4 nanophosphors have been synthesized for the first time in literature by using a poliol-based method at 120 °C from Nd3+ and vanadate precursors. After optimizing the Nd doping level, these phosphors present intense luminescence in the near-infrared biological windows. The X-ray attenuation capacity of the optimum nanophosphor has been found to be higher than that of a commercial X-ray computed tomography contrast agent. After surface coating with polyacrylic acid, such nanoparticles present high colloidal stability in physiological pH medium and high cell viability. Because of these properties, the developed Nd3+-doped LuVO4 nanoparticles have potential applications as a bimodal probe for NIR luminescent bioimaging and X-ray computed tomography.

NIR‐II/III Luminescence Ratiometric Nanothermometry with Phonon‐Tuned Sensitivity

AbstractLuminescence nanothermometers are promising for noninvasive, high resolution thermographics ranging from aeronautics to biomedicine. Yet, limited success has been met in the NIR‐II/III biological windows, which allow temperature evaluation in deep tissues. Herein, a new type of phonon‐based ratiometric thermometry is described that utilizes the luminescence intensity ratio (LIR) between holmium (Ho3+) emission at ≈1190 nm (NIR‐II) and erbium (Er3+) emission at ≈1550 nm (NIR‐III) from a set of oxide nanoparticles of varying host lattices. It is shown that multi‐phonon relaxation in Er3+ ions and phonon‐assisted transfer process in Ho3+ ions play a significant role in LIR determination through channeling the harvested excitation energy to the corresponding emitting states. As a result, temperature sensitivity can be tuned by the dominant phonon energy of host lattice, thus endowing aqueous yttrium oxide (Y2O3, 376 cm−1) nanoparticles to have a relative temperature sensitivity of 1.01% K−1 and absolute temperature sensitivity of 0.0127 K−1 at 65 °C in a physiological temperature range (25–65 °C). And their temperature sensing for biological tissues is further explored and the influence of water and chicken breast on thermometry is discussed. This work constitutes a solid step forward to build sensitive NIR‐II/III nanothermometers for biological applications.

X-ray and UV Excited Long Persistent Luminescence Properties of Zn3Ga2GeO8: Cr3+, Pr3+

Near-infrared long persistent luminescence (NIR-LPL) has attracted increasing attention due to their potential applications in the different fields. The application of different scenes urges us to obtain NIR-LPL under the excitation of different light sources. Herein, we report NIR-LPL phosphors Zn3Ga2GeO8 (ZGGO): Cr3+ and ZGGO: Cr3+, Pr3+, which all shows excellent LPL properties. Either under UV excitation or under X-ray excitation, ZGGO: Cr3+ exhibits NIR-LPL, with emission wavelength at ∼700 nm within the first biological tissue-transparent window (NIR-I: 650–950 nm). Moreover, by co-doping Pr3+, the LPL intensity of ZGGO: Cr3+, Pr3+ is significantly enhanced, and the LPL duration time is also prolonged by 3 times under UV excitation and X-ray excitation. Our results provide the possibility for us to use a single matrix material in different environments.

Visible to near-IR molecular switches based on photochromic indoline spiropyrans with a conjugated cationic fragment.

Photochromic molecules which can absorb and emit light within the "biological window" (650-1450 nm) are of great interest for using in various important biomedical applications such as bio-imaging, photopharmacology, targeted drug delivery, etc. Here we present three new indoline spiropyrans containing conjugated cationic fragments and halogen substituents in the 2H-chromene moiety which were synthesized by a simple one-pot method. The molecular structure of the obtained compounds was confirmed by FT-IR, 1H and 13C NMR spectroscopy (including 2D methods), HRMS, elemental and single crystal X-ray analysis. Photochemical studies revealed the photochromic activity of spiropyrans at room temperature which caused photoswitchable fluorescence in the near-IR region after UV-irradiation. While the spirocyclic forms of compounds demonstrated absorption bands in the UV-Vis spectra with maxima in the visible region at about 445 nm and were not fluorescent, the photogenerated merocyanine isomers absorbed in the near-IR range at 708-738 nm and emitted at 768-791 nm. It was found that compound 1a with fluorine substituent possesses the most red-shifted absorption and emission bands of merocyanine form among all the known photochromic spiropyrans with maxima at 738 and 791 nm correspondingly. TD DFT calculations have shown that the longest wavelength absorption maxima of the merocyanine forms correspond to S0-S1 transitions of the isomers with at least one trans-trans-trans-configured vinylindolium fragment which brings them closer to cyanine-like structure and causes an appearance of the absorption and emission bands in the near-IR region.

Short-wavelength infrared self-assessed photothermal agents based on Ho,Tm:KLu(WO4)2 nanocrystals operating in the third biological window (1.45–1.96 μm wavelength range)

Ho,Tm:KLu(WO4)2 nanoparticles act simultaneously as luminescent nanothermometers and photothermal agents, being self-assessed photothermal agents operating in the third biological window.

An ultrasensitive luminescent nanothermometer in the first biological window based on phonon-assisted thermal enhancing and thermal quenching

The proposed NaYb(MoO4)2:Tm3+ nanothermometer creates a new relative sensitivity record in biological windows with high repeatability and low temperature uncertainty.

X-ray recharged long afterglow luminescent nanoparticles MgGeO3:Mn2+,Yb3+,Li+ in the first and second biological windows for long-term bioimaging.

In this paper, we have designed long afterglow luminescent MgGeO3:Mn2+,Yb3+,Li+ (MGO) nanoparticles in the first (NIR-I) and second (NIR-II) biological windows. Yb3+ ions served not only as the trap center to enhance the NIR-I long afterglow emission of Mn2+ at 680 nm, but also as an emitting center to produce a NIR-II long afterglow emission at ∼1000 nm. Furthermore, we have found the addition of Li+ can greatly increase the NIR-II afterglow emission of Yb3+ and the optimal amount of Mn2+, Yb3+ and Li+ was found to be 0.1, 0.5 and 0.5 mol%, respectively. The MGO nanoparticles synthesized using sol-gel methods showed a uniform morphology with a diameter of 50-100 nm, which were suitable for applications in bioimaging. More importantly, we have found MGO nanoparticles can be effectively excited to produce long persistent NIR-I and II luminescence using soft X-rays, suggesting that low dosage soft X-rays can also serve as a more powerful and deep tissue excitation source to recharge MGO nanoparticles. Furthermore, the MGO nanoparticles can also be re-excited to produce photo-stimulated emission under the irradiation of 650 and 808 nm NIR lasers. The in vivo imaging results have shown that MGO nanoparticles modified with folic acid (FA) can effectively realize super long-term targeted in vivo imaging of inflammation with a high sensitivity via recharging using soft X-rays and NIR lasers, which can provide not only an accurate diagnosis of inflammation, but also long-term monitoring of possible changes in the focus of inflammation in real time.