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.
Two fundamental and unsolved problems facing bioimaging and nanomedicine are nonspecific uptake of intravenously administered diagnostic and/or therapeutic agents by normal tissues and organs, and incomplete elimination of unbound targeted agents from the body. To solve these problems, we have synthesized a series of indocyanine near-infrared (NIR) fluorophores that varied systematically in net charge, conformational shape, hydrophilicity/lipophilicity, and charge distribution. Using 3D molecular modeling and optical fluorescence imaging, we have defined the relationship among the key independent variables that dictate biodistribution and tissue-specific targeting such as lung and sentinel lymph nodes (Nat Biotechnol. 2010), human prostate cancers (Nat Nanotechnol. 2010), and human melanomas (Nat Biotechnol. 2013). Recently, we have developed new pharmacophore design strategy “structure-inherent targeting,” where tissue- and/or organ-specific targeting is engineered directly into the non-resonant structure of a NIR fluorophore, thus creating the most compact possible optical contrast agent for bioimaging and nanomedicine (Angew Chem. 2015, Nat Med. 2015). The biodistribution and targeting of these compounds vary with dependence on their unique physicochemical descriptors and cellular receptors, which permit 1) selective binding to the target tissue/organ, 2) visualization of the target specifically and selectively, and 3) provide curing options such as image-guided surgery or photo dynamic therapy. Our study solves two fundamental problems associated with fluorescence image-guided surgery and lays the foundation for additional targeted agents with optimal optical and in vivo performance.