Low-intensity Near-infrared Light Research Articles

Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.

Dual-function artificial molecular motors performing rotation and photoluminescence.

Molecular machines have caused one of the greatest paradigm shifts in chemistry, and by powering artificial mechanical molecular systems and enabling autonomous motion, they are expected to be at the heart of exciting new technologies. One of the biggest challenges that still needs to be addressed is designing the involved molecules to combine different orthogonally controllable functions. Here, we present a prototype of artificial molecular motors exhibiting the dual function of rotary motion and photoluminescence. Both properties are controlled by light of different wavelengths or by exploiting motors' outstanding two-photon absorption properties using low-intensity near-infrared light. This provides a noninvasive way to both locate and operate these motors in situ, essential for the application of molecular machines in complex (bio)environments.

Constructing ultra-stable photothermal plastics assisted by carbon dots with photocaged reactivity

Constructing ultra-stable photothermal plastics assisted by carbon dots with photocaged reactivity

Abstract P3-02-04: Prediction of breast cancer response to neoadjuvant chemotherapy in different biological breast cancer subtypes using diffuse optical tomography

Abstract Background: Optical-based imaging modalities play an important role in assessing breast tissue composition by measuring optical property contrast from endogenous chromophores. The advantages of optical techniques are the use of non-ionizing radiation, ease of use, and relatively low cost. The primary objective of this study is to examine changes in optically derived parameters (i.e., deoxy-hemoglobin concentration, ctHHb) from different breast cancer subtypes under neoadjuvant chemotherapy (NAC), and correlate with tumor pathologic complete response (pCR). Methods: This retrospective study evaluated 89 tumors in total divided into three distinct subtypes: HR+/HER2- (n=34), HER2+ (n=27), and TNBC (n=28). All patients were imaged at baseline, before starting NAC (TP0), and two weeks after receiving one cycle of taxane-based chemotherapy (TP1). HER2+ breast cancer patients also received HER2-target therapy. pCR was defined as complete absence of invasive carcinoma in the breast and lymph node(s) (ypT0/is ypN0 Mx) at the time of surgery. Whole breast volume was imaged by a diffuse optical tomography breast imaging system (DOTBIS) using low-intensity near-infrared light. ctHHb tumor volume concentration was normalized by the non-affected health tissue ctHHb mean value (ctHHbN). For each molecular subgroup, we conducted an independent-samples t-test to determine if there was a difference in ctHHbN levels at TP1 compared to TP0 between patients with a pCR and non-pCR. Significance was assumed at a confidence interval of 95% (α = 0.05). Results: In total, 69 patients were imaged with DOTIBS at both time points, TP0 and TP1. HR+/HER2-, TNBC and HER2+ accounted for 32% (n=23), 37% (n=22) and 30% (n=22), respectively. The ratio between ctHHbN levels measured at TP1 and TP0 was statistically significantly lower in the pCR group than non-pCR for the HER2+ and HR+/HER2- molecular subgroups, Table 1. Conclusion: Aligned to the current practices in breast cancer management based on the characterization of breast cancer subtypes, our work evaluated changes in DOTBIS optically derived features and pCR status for different subtypes. We observed that ctHHbN levels change after two weeks of NAC and these changes are modifiable according to pCR status and are dependent on immunophenotype. Table 1.Ratio between ctHHbN levels measured at TP1 and TP0 between pCR and non-pCR according to different molecular subtypes.Molecular SubtypepCR (mean ± SD )non-pCR (mean ± SD )p-valueHR+/HER2- (n=23)0.77 ± 0.22 (n=6)1.14 ± 0.24 (n=17).01HER2+ (n=24)0.74 ± 0.30 (n=15)1.54 ± 0.98 (n=9).04TNBC (n=22)0.96 ± 0.38 (n=4)1.29 ± 0.37 (n=18).18Bold values indicate statistical significance at p<.05 level. Citation Format: Mirella L Altoe, Kevin M Kalinsky, Hua Guo, Hanina Hibshoosh, Mariella Tejada, Katherine D Crew, Melissa K Accordino, Meghna S Trivedi, Alessandro Marone, Hyun K Kim, Andreas H Hielscher, Dawn L Hershman. Prediction of breast cancer response to neoadjuvant chemotherapy in different biological breast cancer subtypes using diffuse optical tomography [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-04.

Abstract PS3-10: Monitoring neoadjuvant chemotherapy using diffuse optical tomography breast imaging system

Abstract Background: Optical based imaging modalities have shown promise for monitoring tumor response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. In this study, we evaluate whether changes in deoxy-hemoglobin concentration values acquired by a Diffuse Optical Tomography Breast Imaging System (DOTBIS) over different time points are associated with tumor response. Methods: This is a retrospective evaluation of 55 stage II-III BC patients in the neoadjuvant setting who received weekly paclitaxel x 12, followed by dose-dense adriamycin/cyclophosphamide every 2 weeks x 4. The patients were enrolled in this cohort study between 2011 and 2019, and DOTBIS images were acquired from the patient whole breast volume at 6 different time points: at baseline (TP0); two weeks after the first taxane infusion (TP1); after four infusions of taxane (TP2); at the end of the taxane regimen and before starting AC cycle (TP3); after two AC infusions (TP4); and at the end of NAC and before surgery (TP5). ctHHb tumor concentration was measured using low-intensity near-infrared light and normalized by the non-tumor region ctHHb mean value (ctHHbN). In order to evaluate whether pCR status, menopausal status, and molecular subtype classification influence the change of ctHHbN over time, we designed a multilevel mixed-effect statistical model. pCR was defined as no invasive tumor cells from the breast and axillary tissue at surgery (ypT0 ypN0). Results: 20 patients had pCR and 35 were classified as non-pCR. The estimate average ctHHbN for pCR tumors at baseline was 4.02. There was a significant reduction in ctHHbN levels for pCR group at TP1 (-1.31, p = .0001) and TP2 (-1.36, p = .0416). Changes in ctHHbN levels compared to baseline (TP0) values were statistically significant different between pCR and non-pCR at all time points except at the end of the taxane cycle (TP3), Table 1. No significant changes over time were identified between molecular subtypes groups, or between pre- and post-menopausal status. Conclusions: Our study adds to the body of evidence reported for diffuse optical imaging methods applied to breast cancer treatment response. These results show that DOTBIS measured features, such as ctHHbN, change in accordance with pCR status after 2 weeks under NAC, and there are differences in time evolution between the pCR groups. Reduction in ctHHbN levels represents the chemotherapeutic- induced changes in the tumor microvasculature: lower ctHHbN values associate with the reduction in tumor cell proliferation, and consequently in oxygen consumption. Future studies are warranted to evaluate whether early response prediction might determine if earlier treatment changes alter patient outcome. Table 1 - Changes in ctHHbN levels compared to baseline (TP0) values between pCR and non-pCR at all imaging time points. Bold values indicate statistical significance at p <.05 level.Time PointMean Difference ± Std. Errorp-valueTP11.92 ± 0.400.0000TP22.04 ± 0.820.0145TP30.83 ± 1.030.4198TP42.71 ± 0.870.0021TP52.63 ± 0.900.0037 Citation Format: Mirella L Altoe, Kevin Kalinsky, Hua Guo, Hanina Hibshoosh, Mariella Tejada, Katherine D Crew, Melissa K Accordino, Meghna Trivedi, Alessandro Marone, Hyun K Kim, Andreas H Hielscher, Dawn L Hershman. Monitoring neoadjuvant chemotherapy using diffuse optical tomography breast imaging system [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-10.

Powering rotary molecular motors with low-intensity near-infrared light.

Light-controlled artificial molecular machines hold tremendous potential to revolutionize molecular sciences as autonomous motion allows the design of smart materials and systems whose properties can respond, adapt, and be modified on command. One long-standing challenge toward future applicability has been the need to develop methods using low-energy, low-intensity, near-infrared light to power these nanomachines. Here, we describe a rotary molecular motor sensitized by a two-photon absorber, which efficiently operates under near-infrared light at intensities and wavelengths compatible with in vivo studies. Time-resolved spectroscopy was used to gain insight into the mechanism of energy transfer to the motor following initial two-photon excitation. Our results offer prospects toward in vitro and in vivo applications of artificial molecular motors.

Single-Cell Photothermal Neuromodulation for Functional Mapping of Neural Networks.

Photothermal neuromodulation is one of the emerging technologies being developed for neuroscience studies because it can provide minimally invasive control of neural activity in the deep brain with submillimeter precision. However, single-cell modulation without genetic modification still remains a challenge, hindering its path to broad applications. Here, we introduce a nanoplasmonic approach to inhibit single-neural activity with high temporal resolution. Low-intensity near-infrared light was focused at the single cell size on a gold-nanorod-integrated microelectrode array platform, generating a photothermal effect underneath a target neuron for photothermal stimulation. We found that the photothermal stimulation modulates the spontaneous activity of a target neuron in an inhibitory manner. Single neuron inhibition was fast and highly reliable without thermal damage, and it can induce changes in network firing patterns, potentially suggesting their application for in vivo circuit modulation and functional connectomes.

Stabilization of High Oxidation State Upconversion Nanoparticles by N-Heterocyclic Carbenes.

The stabilization of high oxidation state nanoparticles by N-heterocyclic carbenes is reported. Such nanoparticles represent an important subset in the field of nanoparticles, with different and more challenging requirements for suitable ligands compared to elemental metal nanoparticles. N-Heterocyclic carbene coated NaYF4 :Yb,Tm upconversion nanoparticles were synthesized by a ligand-exchange reaction from a well-defined precursor. This new photoactive material was characterized in detail and employed in the activation of photoresponsive molecules by low-intensity near-infrared light (λ=980 nm).

Upconverting-nanoparticle-assisted photochemistry induced by low-intensity near-infrared light: how low can we go?

Upconverting nanoparticles (UCNPs) convert near-infrared (NIR) light into UV or visible light that can trigger photoreactions of photosensitive compounds. In this paper, we demonstrate how to reduce the intensity of NIR light for UCNP-assisted photochemistry. We synthesized two types of UCNPs with different emission bands and five photosensitive compounds with different absorption bands. A λ=974 nm laser was used to induce photoreactions in all of the investigated photosensitive compounds in the presence of the UCNPs. The excitation thresholds of the photoreactions induced by λ=974 nm light were measured. The lowest threshold was 0.5 W cm(-2) , which is lower than the maximum permissible exposure of skin (0.726 W cm(-2) ). We demonstrate that low-intensity NIR light can induce photoreactions after passing through a piece of tissue without damaging the tissue. Our results indicate that the threshold for UCNP- assisted photochemistry can be reduced by using highly photosensitive compounds that absorb upconverted visible light. Low excitation intensity in UCNP-assisted photochemistry is important for biomedical applications because it minimizes the overheating problems of NIR light and causes less photodamage to biomaterials.

Low-Noise, High-Gain Transimpedance Amplifier Integrated With SiAPD for Low-Intensity Near-Infrared Light Detection

A fully integrated near-infrared spectroscopy photoreceiver including two new silicon avalanche photodiodes (SiAPDs) and a new transimpedance amplifier (TIA) is proposed in this paper. SiAPDs are designed in p+/n-well structure with guard-rings realized in different shapes. The TIA front-end has been designed using distributed-gain concept combined with resistive-feedback and common-gate topology to reach low-noise, low-power consumption, high gain-bandwidth product characteristics and it is robust against power-supply variation (1-3 V). This circuit is developed using 0.35 μm CMOS technology and the measurement results are compared with other results from the literature. The designed rectangular and octagonal SiAPDs have the avalanche gain of 100 and 45 with the breakdown voltage of 9 and 6 V and the photon absorption efficiency of 45% and 25% at 800 nm. Fabricated TIA offers high-transimpedance gain (up to 250 MV/A), tunable BW (1 kHz-1 GHz), extremely low input and output noises (100 fA/√Hz, 1.8 μV/√Hz), and low-power consumption (0.8 mW). The impact and effects of on-chip integration of SiAPD and TIA front-end have been also measured and evaluated.

GaAs devices with vertical and planar structures for optically activated high-voltage switching

A class of semi-insulating gallium arsenide diodes has been manifactured and tested, with a Schottky contact and a special ohmic contact on the back, which can be operated in reverse bias well above 5 V/μm were leakage currents are in the 1–10 μA range (for 3 mm diodes). Preliminary measurements show their feasibility as PhotoConductive Semiconductor Switches (PCSS). At fixed high-voltage bias, the current drawn by this device can be increased at least by two orders of magnitude, by illuminating the diode with low-intensity near-infrared light. The resulting change in resistance can be used in order to switch off (DC mode) the high voltage either in a series or a parallel load configuration. Measurements are reported for 3 mm diameter GaAs diodes, 0.2 mm thick, as for: current–voltage characteristics, current increase upon illumination with a 880 nm LED, linearity of photocurrent vs. illumination level. In addition to these diodes with vertical structure, special GaAs switches with a planar structure have been developed and tested at 670 nm with a focused laser diode beam; they are made of a 0.2 mm substrate and a series of two Schottky contacts facing each other on the same side of the substrate. The planar structures enable multiple independent switches on the same substrate, each one being able to withstand a voltage bias as high as 700 V with typical leakage currents below 20 nA, and in addition, they may provide a photocurrent/dark current gain as high as 10 6. Both types of devices can be activated either locally or remotely, e.g. with illumination via single or multiple optical fibers, thus providing a special type of PCSS for optically controlled high-voltage DC switching. We plan to use devices of this type in high-energy physics experiments, specifically, in order to control remotely the high-voltage bias of microstrip gas chambers.