Low-power Near-infrared Laser Research Articles

Making the Brightest Ones Dim: Maximizing the Photothermal Conversion Efficiency of BODIPY-Based Photothermal Agents.

The successful implementation of photothermal therapy (PTT) in cancer treatment hinges on the development of highly effective photothermal agents (PTAs). Boron dipyrromethene (BODIPY) dyes, being well known for their high brightness and quantum efficiencies, are the antithesis of PTAs. Nonetheless, a systematic exploration of the photophysics and photothermal characteristics of a series of π-extended BODIPY dyes with high absorptivity in the near-infrared (NIR) region has achieved superior photothermal conversion efficiencies (>90%), in both monomeric state and nanoparticles after encapsulation in a biocompatible polyethyleneglycol 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000]. Optimal PTA candidates combine strong NIR absorption provided by extended donor-acceptor conjugation and an optimization of the electronic and steric effects of meso-substituents to maximize photothermal conversion performance. The PTT-optimized meso-CF3-BODIPY, TCF3PEn exhibits exceptional efficacy in inducing cancer cell apoptosis and in vivo tumor ablation using low-power NIR laser irradiation (0.3 Wcm-2, 808 nm) as well as excellent biological safety, underscoring its potential for advancing light-induced cancer therapies.

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS.

The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury. This is a preclinical proof-of-concept study to determine the therapeutic effect of transcranial treatment with a low-power near-infrared laser in a mouse model of ischemic stroke. The laser treatment was performed before the middle cerebral artery occlusion with a filament. To determine the involvement of eNOS phosphorylation, unphosphorylatable eNOS S1176A knock-in mice were used. Each measurement was analyzed by a 2-way ANOVA to assess the effect of the treatment on cerebral blood flow with laser Doppler flowmetry, eNOS phosphorylation by immunoblot analysis, and stroke outcomes by infarct volumes and neurological deficits. Pretreatment with a 1064-nm laser at an irradiance of 50 mW/cm2 improved cerebral blood flow, eNOS phosphorylation, and stroke outcomes. Near-infrared II photobiomodulation could offer a noninvasive and low-risk adjunctive therapy for stroke injury. This new modality using a physical parameter merits further consideration to develop innovative therapies to prevent and treat a wide array of cardiovascular diseases.

Near-Infrared Light Triggered a High Temperature Utilizing Donor-Acceptor Cocrystals.

Developing a suitable initiation for the energetic materials that respond to a low-power near-infrared laser can aid in replacing the current expensive and bulky laser-initiation systems. Here, we report on a system of molecularly tailored 1:1 donor-acceptor (D-A) charge-transfer (CT) cocrystals that manifest ultrabroad absorption (200-2500 nm) characteristics as well as noteworthy very fast self-assembly behaviors. The very narrow highest occupied molecular orbital-lowest unoccupied molecular orbital gap enables N,N,N',N'-tetramethyl-p-phenylenediamine and tetrahalo-1,4-benzoquinones (TMPD-TXBQ) cocrystals to have a great light-harvesting ability in the near-infrared range. When irradiated with a low-power hand-held 808 nm laser with an input energy of only 40 mJ or a power density of 260 mW·cm-2, these TMPD-TXBQ cocrystals immediately undergo an efficient photothermal conversion followed by a dramatic exothermic thermal polymerization reaction due to the face-to-face D-A-D-A stacking in these cocystals to achieve a temperature as high as 318.9 °C. This temperature is high enough for a thermal initiation of most common energetic materials, and thus this TMPD-TXBQ cocrystal can potentially act as a near-infrared laser initiator that is compact, lightweight, and cost-effective.

Lung cancer photothermal ablation by low-power near-infrared laser and topical injection of indocyanine green.

Surgical treatment is the gold standard for the treatment of early-stage non-small-cell lung cancer. However, minimally invasive tumour ablation can be an alternative treatment for patients not eligible for surgery due to comorbidities. The aim of this study was to evaluate the efficacy of photothermal ablation therapy using low-power near-infrared laser and topical injection of indocyanine green (ICG), a photosensitizer, in a preclinical study using a rabbit VX2 lung cancer model. Six New Zealand white rabbits were used. Five hundred microlitres of a suspension containing 0.5 × 107 VX2 cancer cells with growth factor-reduced Matrigel was inoculated into the right lung using an ultrathin bronchoscope. Three rabbits were treated with laser ablation therapy with topical injection of ICG, whereas another 3 rabbits were treated with laser ablation alone. All tumours were irradiated with a laser with 500-mW output at 808 nm for 15 min. The tumours were examined histopathologically to assess the state of ablation. The maximum tumour surface temperatures in rabbits treated using ICG/laser and laser alone were higher than 58°C and lower than 40°C, respectively. The ablated areas in the rabbits treated with ICG/laser were significantly larger than those in the rabbits treated with laser alone (0.49 ± 0.27 vs 0.02 ± 0.002 cm2, respectively) (P < 0.05). The photothermal treatment using the combination of low-power near-infrared laser and topical injection of ICG can ablate a larger tumour area than laser treatment alone.

A Wearable Fiberless Optical Sensor for Continuous Monitoring of Cerebral Blood Flow in Mice.

Continuous and longitudinal monitoring of cerebral blood flow (CBF) in animal models provides information for studying the mechanisms and interventions of various cerebral diseases. Since anesthesia may affect brain hemodynamics, researchers have been seeking wearable devices for use in conscious animals. We present a wearable diffuse speckle contrast flowmeter (DSCF) probe for monitoring CBF variations in mice. The DSCF probe consists of a small low-power near-infrared laser diode as a point source and an ultra-small low-power CMOS camera as a 2D detector array, which can be affixed on a mouse head. The movement of red blood cells in brain cortex (i.e., CBF) produces spatial fluctuations of laser speckles, which are captured by the camera. The DSCF system was calibrated using tissue phantoms and validated in a human forearm and mouse brains for continuous monitoring of blood flow increases and decreases against the established technologies. Significant correlations were observed among these measurements (R2 ≥ 0.80, p < 10-5). This small fiberless probe has the potential to be worn by a freely moving conscious mouse. Moreover, the flexible source-detector configuration allows for varied probing depths up to ~8 mm, which is sufficient for transcranially detecting CBF in the cortices of rodents and newborn infants.

Brillouin microscopy: assessing ocular tissue biomechanics.

Purpose of reviewAssessment of corneal biomechanics has been an unmet clinical need in ophthalmology for many years. Many researchers and clinicians have identified corneal biomechanics as source of variability in refractive procedures and one of the main factors in keratoconus. However, it has been difficult to accurately characterize corneal biomechanics in patients. The recent development of Brillouin light scattering microscopy heightens the promise of bringing biomechanics into the clinic. The aim of this review is to overview the progress and discuss prospective applications of this new technology.Recent findingsBrillouin microscopy uses a low-power near-infrared laser beam to determine longitudinal modulus or mechanical compressibility of tissue by analyzing the return signal spectrum. Human clinical studies have demonstrated significant difference in the elastic properties of normal corneas versus corneas diagnosed with mild and severe keratoconus. Clinical data have also shown biomechanical changes after corneal cross-linking treatment of keratoconus patients. Brillouin measurements of the crystalline lens and sclera have also been demonstrated.SummaryBrillouin microscopy is a promising technology under commercial development at present. The technique enables physicians to characterize the biomechanical properties of ocular tissues.

P1.12-003 Photothermal Ablation of Lung Cancer by Low Power Near-Infrared Laser and Topical Injection of Indocyanine Green; A Preliminary Animal Study

P1.12-003 Photothermal Ablation of Lung Cancer by Low Power Near-Infrared Laser and Topical Injection of Indocyanine Green; A Preliminary Animal Study

Transdermal thiol-acrylate polyethylene glycol hydrogel synthesis using near infrared light.

Light-induced polymerization has been widely applied for hydrogel synthesis, which conventionally involves the use of ultraviolet or visible light to activate a photoinitiator for polymerization. However, with these light sources, transdermal gelation is not efficient and feasible due to their substantial interactions with biological systems, and thus a high power is required. In this study, we used biocompatible and tissue-penetrating near infrared (NIR) light to remotely trigger a thiol-acrylate reaction for efficient in vivo gelation with good controllability. Our gelation system includes gold nanorods as a photothermal agent, a thermal initiator, diacrylate polyethylene glycol (PEG), and thiolated PEG. Irradiation with a low-power NIR laser (0.3 W cm(-2)) could induce gelation via a mixed-mode reaction with a small increase in temperature (∼5 °C) under the optimized conditions. We also achieved successful transdermal gelation via the NIR-assisted photothermal thiol-acryl reactions. This new type of NIR-assisted thiol-acrylate polymerization provides new opportunities for in situ hydrogel formation for injectable hydrogels and delivery of drugs/cells for various biomedical applications.

Photothermal ablation of human lung cancer by low-power near-infrared laser and topical injection of indocyanine green.

The present study was designed to evaluate the efficacy of photothermal ablation therapy for lung cancer by low-power near-infrared laser and topical injection of indocyanine green (ICG). In vitro study 1: an 808 nm laser with 250 mW was irradiated for 10 minutes using different dilutions of ICG and the temporal thermal effect was monitored. ICG (1 mL of 0.5 g/L) was heated to a temperature of >30°C from the base temperature by laser irradiation. In vitro study 2: the cytotoxic effect of hyperthermia on human lung cancer cells was examined in different temperature and time settings. Cell viability was quantified by both an MTS assay and reculturing. Fatal conditions evaluated by reculturing were as follows: thermal treatment at 55°C for 5 minutes, 53°C for 10 minutes, and 51°C for 15 minutes. The MTS assay study suggested that thermal treatment at 59°C for 5 minutes and 57°C for 20 minutes showed a severe cytotoxic effect. In vivo study: nude mouse subcutaneous NCI-H460 human lung cancer xenograft models were used for the study. Saline or 0.5 g/L of ICG was injected topically into the tumor (n=3/group). Tumors were irradiated with a laser at 500 mW for 10 minutes. Although the tumor diameter reached 1 cm within 24 days after treatment in all 3 mice using saline/laser, tumor sizes were gradually reduced in all 3 mice using the ICG/laser. In 2 of the 3 mice using ICG/laser, tumors had disappeared macroscopically. The efficacy of the photothermal ablation therapy by low-power near-infrared laser and a topical injection of ICG was clarified using a mouse subcutaneous a lung cancer xenograft model.

Core–shell–shell nanorods for controlled release of silver that can serve as a nanoheater for photothermal treatment on bacteria

A novel bactericidal material comprising rod-shaped core–shell–shell Au–Ag–Au nanorods is constructed as a nanoheater in the near-infrared (NIR) region. The outer Au shell melts under laser irradiation and results in exposure of the inner Ag shell, facilitating the controlled release of the antibacterial Ag shell/layer or Ag+. This results in the Au–Ag–Au nanorods having a favorable bactericidal ability as it combines the features of physical photothermal ablation sterilization of the outer Au shell and the antibacterial effect of the inner Ag shell or Ag+ to the surrounding bacteria. The sterilizing ability of Au–Ag–Au nanorods is investigated with Escherichia coli O157:H7 as a model bacterial strain. Under low-power NIR laser irradiation (785nm, 50mWcm−2), the Au–Ag–Au nanoheater exhibits a higher photothermal conversion efficiency (with a solution temperature of 44°C) with respect to that for the Au–Ag nanorods (39°C). Meanwhile, a much improved stability with respect to Au–Ag nanorods is observed, i.e., 16 successive days of monitoring reveal virtually no change in the ultraviolet–visible spectrum of Au–Ag–Au nanorods, while a significant drop in absorption along with a 92nm red shift of Localized Surface Plasmon Resonance is recorded for the Au–Ag nanorods. This brings an increasing bactericidal efficiency and long-term stability for the Au–Ag–Au nanorods. At a dosage of 10μgml−1, a killing rate of 100% is reached for the E. coli O157:H7 cells under 20min of irradiation. The use of Au–Ag–Au nanorods avoids the abuse of broad-spectrum antibiotics and reduces the damage of tissues by alleviating the toxicity of silver under controlled release and by the use of low-power laser irradiation. These features could make the bimetallic core–shell–shell nanorods a favorable nanoheater for in vivo biomedical applications.

Near Infrared Tunable Gold Nanoparticles for Low Power Laser Ablation of Esophageal Adenocarcinoma

ABSTRACTGold nanoparticles (GNPs) with precisely controlled near infrared (NIR) absorption were synthesized by one-step reaction of chloroauric acid and sodium thiosulfate. The NIR absorption wavelengths and average particle size increase with increasing molar ratio of HAuCl4/Na2S2O3. The as-synthesized GNPs consist of different shape and size, including small spherical gold colloids and larger non-spherical gold crystals. The GNPs with good chemical and optical stability only form in a suitable range of the HAuCl4/Na2S2O3 molar ratio. High molar ratio of HAuCl4/Na2S2O3 reduces GNPs stability due to Ostwald ripening. Chitosan coating improves particle stability and allows these GNPs effective ablation for esophageal adenocarcinoma under low power NIR laser radiation.

Gold/Chitosan Nanocomposites with Specific Near Infrared Absorption for Photothermal Therapy Applications

Gold/chitosan nanocomposites were synthesized and evaluated as a therapeutic agent for the photothermal therapy. Gold nanoparticles (Au NPs) with controllable optical absorption in the near infrared (NIR) region were prepared by the reaction of chloroauric acid and sodium thiosulfate. To apply these particles to cancer therapy, the bare Au NPs were coated with chitosan (CS), O‐carboxymethyl chitosan (CMCS), and a blend of CS and CMCS for utilizations in physiologic conditions. The surface properties, optical stability, and photothermal ablation efficiency on hepatocellular carcinoma cells (HepG2) and human dermal fibroblast cells (HDF) demonstrate that these gold nanocomposites have great potential as a therapeutic agent in in vitro tests. The CS‐coated nanocomposites show the highest efficiency for the photo‐ablation on the HepG2 cells, and the CS and CMCS blended coated particles show the best discrimination between the cancer cell and normal cells. The well‐controlled NIR absorption and the biocompatible surface of these nanocomposites allow low‐power NIR laser activation and low‐dosage particle injection for the cancer cell treatment.

Graphene in Mice: Ultrahigh In Vivo Tumor Uptake and Efficient Photothermal Therapy

Although biomedical applications of carbon nanotubes have been intensively studied in recent years, its sister, graphene, has been rarely explored in biomedicine. In this work, for the first time we study the in vivo behaviors of nanographene sheets (NGS) with polyethylene glycol (PEG) coating by a fluorescent labeling method. In vivo fluorescence imaging reveals surprisingly high tumor uptake of NGS in several xenograft tumor mouse models. Distinctive from PEGylated carbon nanotubes, PEGylated NGS shows several interesting in vivo behaviors including highly efficient tumor passive targeting and relatively low retention in reticuloendothelial systems. We then utilize the strong optical absorbance of NGS in the near-infrared (NIR) region for in vivo photothermal therapy, achieving ultraefficient tumor ablation after intravenous administration of NGS and low-power NIR laser irradiation on the tumor. Furthermore, no obvious side effect of PEGylated NGS is noted for the injected mice by histology, blood chemistry, and complete blood panel analysis in our pilot toxicity study. Although a lot more efforts are required to further understand the in vivo behaviors and the long-term toxicology of this new type of nanomaterials, our work is the first success of using carbon nanomaterials for efficient in vivo photothermal therapy by intravenous administration and suggests the great promise of graphene in biomedical applications, such as cancer treatment.

Toward Self-Assembly of Nanoparticles on Polymeric Microshells: Near-IR Release and Permeability

We present a novel approach to construct hollow polymeric microcontainers that can be remotely addressed using a low-power near-infrared laser to release encapsulated materials. Microshells possessing walls with aggregates of gold nanoparticles are found to release encapsulated materials upon near-IR irradiation, while shells containing the same amount of nonaggregated gold nanoparticles did not release their contents. The permeability of thermally shrunk microcapsules to dextran molecules is the lowest for shells containing nonaggregated nanoparticles and the highest for microcapsules with no nanoparticles. The wall thickness, roughness, influence of concentration of encapsulated materials, and general shrinking behavior of the microcapsules are studied. Aggregation of nanoparticles increases the absorption coefficient in the near-infrared part of electromagnetic spectrum. The temperature increase upon near-infrared laser illumination for different gold nanoparticle distributions is simulated. Important implications of this approach are expected in development of drug delivery systems as well as in temperature- and light-sensitive materials and membranes.

Efficient phase-matched second-harmonic generation of blue light in an organic waveguide

THE development of materials for the efficient frequency-doubling of low-power semiconductor lasers is a technologically important goal for which several important challenges remain. The ease of processing and high intrinsic optical nonlinearity of organic materials1,2 makes them attractive for such applications, and it has been demonstrated that molecular-assembly techniques can achieve the macroscopic non-centrosymmetric order required for bulk nonlinear optical activity3,4. But to achieve efficient power conversion, a promising material must also exhibit low attenuation of light at high power densities, and match phase velocities over relatively long distances for light at the fundamental and second-harmonic frequencies5. Here we report the fabrication by Langmuir– Blodgett deposition of a low-loss optical waveguide in which precise control of the film thickness, together with inversion of the nonlinear susceptibility across the film, are used to simultaneously achieve phase matching and improve the optical–field overlap between the propagating (fundamental and second-harmonic) waveguide modes. The resulting structure converts low-power near-infrared laser light efficiently to blue light.