Photobiomodulation also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infrared region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential, and adenosine triphosphate production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium (Ca2+) to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO, and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, and antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.

At a nano-level, optical properties of gold are unique and gave birth to an emerging platform of nanogold-based systems for diverse applications, because gold nanoparticle properties are tunable as a function of size and shape. Within the available techniques for the synthesis of gold nanoparticles, the radiolytic synthesis allows proper control of the nucleation process without the need for reducing agents, in a single step, combined or not with simultaneous sterilization. This review details and summarizes the use of radiation technologies for the synthesis and preparation of gold nanoparticles concerning fundamental aspects, mechanism, current pathways for synthesis and radiation sources, as well as briefly outlines final applications and some toxicity aspects related to nanogold-based systems.

Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naïve mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients.

Low-level light therapy (or photobiomodulation therapy) is a rapidly growing approach to treating a wide range of diseases and disorders that afflict humanity. This Tutorial Text covers the basic molecular and cellular mechanisms of action, applications for treating diseases in animal models, and its use in clinical trials and therapeutic practice in patients. Other topics include the two basic chromophores and how they trigger the signaling pathways, activation of transcription factors, and mobilization of stem cells; how the light-source design and the relevant energy parameters can affect the outcome of therapy; and the physics and tissue-optics principles that concern LLLT.