We investigated the “laser adjuvant” that improved vaccine efficacy, via combining non-invasive near-infrared red (NIR) light irradiation and intradermal influenza vaccine and discovered the crucial role of reactive oxygen species (ROS) and mast cells. This study elucidates the effects of a new wavelength (1270 nm) of NIR light that exhibits a similar adjuvant effect at lower energy on mast cells and mouse skin, revealing ROS and ATP production via mitochondrial photoreception, increased chemokine mRNA expression, and durable antibody titers in immunized mice. These findings highlight the clinical potential of 1270 nm NIR light, demonstrating the wavelength-specific effect of laser adjuvants.
Photobiomodulation (PBM) using near-infrared (NIR)-II light has been shown to enhance anti-cancer immunity by reducing oxidative stress, promoting proliferation, and reducing PD-1 expression in tumor-infiltrating CD8+ T cells, ultimately suppressing tumor progression. Meanwhile, photoimmunotherapy (PIT) using NIR light has also shown promise in cancer treatment, inducing a strong anti-cancer immune response. Combining PBM with laser-based phototherapy, including PIT, could have the potential to amplify their therapeutic effects maximally, offering a promising avenue for developing safe and effective cancer therapies.
Photobiomodulation (PBM) with low-power near-infrared (NIR) light has shown diverse beneficial effects. Recent studies report that PBM also increases bioavailable nitric oxide (NO), which is a critical gaseous mediator for various physiological processes and could be used to treat cardiovascular and cerebrovascular diseases with suppressed endothelial NO production. We explored using NIR-II light (1000-1700 nm) for PBM. NIR-II laser treatment efficiently enhanced NO generation in endothelial cells. Since impaired NO production is also associated with neurological diseases, this novel therapy could be further explored to treat diseases such as traumatic brain injury, sleep disorders, and Alzheimer's disease.
While ICG-based NIR imaging has shown great potential in intraoperative surgery, there are two fundamental and unsolved problems facing medical imaging: 1) nonspecific uptake of intravenously administered diagnostic and/or therapeutic agents by normal tissues and organs and 2) incomplete elimination of unbound targeted agents from the body. These problems make image-guided cancer surgery extremely difficult because the background signal is high, and therefore the TBR is low. Designing a targeted contrast agent that shows fast clearance from the background tissues and eventually from the body after complete targeting is the key to the success of image-guided interventions. “Structure-Inherent Targeting” is a strategy that combines tissue-specific targeting components and imaging domain into a single molecule for targeting and imaging specific tissues in real-time, where the compact structural design enables the unbound contrast agent to be easily cleared from the body after targeting.
Although immunotherapy, including immune checkpoint inhibitors, has revolutionized cancer treatment, only a small percentage of patients show sustained response. Recently, we have shown that photobiomodulation (PBM) with near-infrared (NIR) light in the NIR-II window reduces oxidative stress and supports CD8+ T cell proliferation, suggesting that PBM with NIR-II light may enhance anticancer immunity. In this study, we report a novel approach to support tumor-infiltrating CD8+ T cells by PBM using NIR-II laser with high tissue penetration depth. Lasers are a safe and low-cost therapy that can be used in combination with a broad range of other therapies without modification.
There is solid evidence of diverse beneficial effects of the treatment with low-power near-infrared (NIR) light in the NIR I window (630-900 nm). We have demonstrated PBM with NIR-II window (1061-1301 nm) augments the immune response of the vaccine, but other beneficial effects of NIR-II laser have not been fully explored. In this study, we have shown that NIR-II laser enhances bioavailable NO in endothelial cells. Since a hallmark of endothelial dysfunction is suppressed eNOS with concomitant NO deficiency, NIR-II laser technology could be broadly used to restore endothelial NO and treat or prevent cardiovascular diseases.
Since biological chromophores typically show several absorption peaks, the specific effects of photobiomodulation would be induced with a combination of two wavelengths, rather than a single wavelength of near-infrared (NIR) light.
Single cell live imaging of T cells treated with a combination of 1064 and 1270 nm NIR lasers revealed that the treatment modulated intracellular calcium and reactive oxygen species (ROS) in T cells, which are known to be critical regulators of their function.
The treatment with a specific combination of NIR wavelengths of low power laser could be further explored for therapeutic purposes including immunotherapy for cancer and allergy.
The incorporation of an immunologic adjuvant to enhance the immune response is a standard practice for modern vaccines. In the past decade, researchers have consistently reported a new approach to augment the immune response to vaccine by brief treatment of the skin with laser light without appreciable adverse effects. To date, four classes of laser adjuvant have been established. Amongst these, pulsed and non-pulsed laser adjuvant merit further development because of their established efficacy and safety in animal models. Such a technology offers a valuable choice of immunologic adjuvant for accelerated vaccine development against emerging infectious diseases including COVID-19.
Accurate mapping of gastrointestinal stromal tumors (GIST) during surgery is difficult, which contributes to the suboptimal diagnosis and recurrence of cancers. To overcome this limitation, we developed a near-infrared (NIR) fluorescent nanoprobe for real-time navigation of GIST using a targeted strategy against the CD117 ligand stem cell factor (SCF). A zwitterionic NIR fluorophore conjugated to SCF showed specific binding to a xenograft mouse model of CD117-positive GIST-T1 with minimal nonspecific tissue signals. This promising intraoperative imaging strategy could be further explored for early diagnosis and follow-up of GIST prognosis before and after surgical resection.
There remains a paucity of methodological tools to determine the biodistribution of vaccine antigens. In response to this, we established a near-infrared (NIR) imaging method using a NIR fluorophore, ZW800-1C, conjugated with different sizes of vaccine antigens that allows for real-time monitoring of the fate of delivered vaccines in vivo. The fluorescent signal observed using the system after a model vaccine injection in mice recapitulated the size-dependent transport of the vaccine into the secondary lymphoid tissue. This methodology can be broadly applied for optimization of formulations and safety evaluation of clinical vaccines.
Significance: Photobiomodulation is a well-established therapeutic modality. However, the mechanism of action is poorly understood, due to lack of research in the causal relationship between the near-infrared (NIR) light irradiation and its specific biological effects, hindering broader applications of this technology.
Aim: Since biological chromophores typically show several absorption peaks, we determined whether specific effects of photobiomodulation are induced with a combination of two wavelengths at a certain range of irradiance only, rather than a single wavelength of NIR light.
Approach: In order to analyze a wide array of combinations of multispectral NIR light at various irradiances efficiently, we developed a new optical platform equipped with two distinct wavelengths of NIR lasers by high-throughput multiple dosing for single-cell live imaging. Two wavelengths of 1064 and 1270 nm were selected based on their photobiomodulatory effects reported in the literature.
Results: A specific combination of wavelengths at low irradiances (250 to 400 mW / cm2 for 1064 nm and 55 to 65 mW / cm2 for 1270 nm) modulates mitochondrial retrograde signaling, including intracellular calcium and reactive oxygen species in T cells. The time-dependent density functional theory computation of binding of nitric oxide (NO) to cytochrome c oxidase indicates that the illumination with NIR light could result in the NO release, which might be involved in these changes.
Conclusions: This optical platform is a powerful tool to study causal relationship between a specific parameter of NIR light and its biological effects. Such a platform is useful for a further mechanistic study on not only photobiomodulation but also other modalities in photomedicine.
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