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.
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.
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.
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.