Photodynamic therapy (PDT) has been applied to treat a wide range of medical conditions, including wet age-related macular degeneration psoriasis, atherosclerosis, viral infection and malignant cancers. However, the tissue penetration limitation of excitation light hinders the widespread clinical use of PDT. To overcome this “Achilles' heel”, deep PDT, a novel type of phototherapy, has been developed for the efficient treatment of deep-seated diseases. Based on the different excitation sources, including near-infrared (NIR) light, X-ray radiation, and internal self-luminescence, a series of deep PDT techniques have been explored to demonstrate the advantages of deep cancer therapy over conventional PDT excited by ultraviolet-visible (UV-Vis) light. In particular, the featured applications of deep PDT, such as organelle-targeted deep PDT, hypoxic deep PDT and deep PDT-involved multimodal synergistic therapy are discussed. Finally, the future development and potential challenges of deep PDT are also elucidated for clinical translation. It is highly expected that deep PDT will be developed as a versatile, depth/oxygen-independent and minimally invasive strategy for treating a variety of malignant tumours at deep locations.

Overcoming the Achilles' heel of photodynamic therapy.

Low-level laser (light) therapy (LLLT) is a fast-growing technology used to treat a multitude of conditions that require stimulation of healing, relief of pain and inflammation, and restoration of function. Although the skin is the organ that is naturally exposed to light more than any other organ, it still responds well to red and near-infrared wavelengths. The photons are absorbed by mitochondrial chromophores in skin cells. Consequently electron transport, adenosine triphosphate (ATP) nitric oxide release, blood flow, reactive oxygen species increase and diverse signaling pathways get activated. Stem cells can be activated allowing increased tissue repair and healing. In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT can reduce UV damage both as a treatment and as a prophylaxis. In pigmentary disorders such as vitiligo, LLLT can increase pigmentation by stimulating melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity. Inflammatory diseases such as psoriasis and acne can also benefit. The non-invasive nature and almost complete absence of side-effects encourages further testing in dermatology.

Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring.

Although conventional antimicrobial drugs have been viewed as miraculous cure-alls for the past 80 years, increasing antimicrobial drug resistance requires a major and rapid intervention. However, the development of novel but still conventional systemic antimicrobial agents, having only a single mode or site of action, will not alleviate the situation because it is probably only a matter of time until any such agents will also become ineffective. To continue to produce new agents based on this notion is unacceptable, and there is an increasing need for alternative approaches to the problem. By contrast, light-activated molecules called photoantimicrobials act locally via the in-situ production of highly reactive oxygen species, which simultaneously attack various biomolecular sites in the pathogenic target and therefore offer both multiple and variable sites of action. This non-specificity at the target circumvents conventional mechanisms of resistance and inhibits the development of resistance to the agents themselves. Photoantimicrobial therapy is safe and easy to implement and, unlike conventional agents, the activity spectrum of photoantimicrobials covers bacteria, fungi, viruses, and protozoa. However, clinical trials of these new, truly broad-spectrum, and minimally toxic agents have been few, and the funding for research and development is almost non-existent. Photoantimicrobials constitute one of the few ways forward through the morass of drug-resistant infectious disease and should be fully explored. In this Personal View, we raise awareness of the novel photoantimicrobial technologies that offer a viable alternative to conventional drugs in many relevant application fields, and could thus slow the pace of resistance development.

Photoantimicrobials-are we afraid of the light?

Photobiomodulation (PBM) involves the use of red or near-infrared light at low power densities to produce a beneficial effect on cells or tissues. PBM therapy is used to reduce pain, inflammation, edema, and to regenerate damaged tissues such as wounds, bones, and tendons. The primary site of light absorption in mammalian cells has been identified as the mitochondria and, more specifically, cytochrome c oxidase (CCO). It is hypothesized that inhibitory nitric oxide can be dissociated from CCO, thus restoring electron transport and increasing mitochondrial membrane potential. Another mechanism involves activation of light or heat-gated ion channels. This review will cover the redox signaling that occurs in PBM and examine the difference between healthy and stressed cells, where PBM can have apparently opposite effects. PBM has a marked effect on stem cells, and this is proposed to operate via mitochondrial redox signaling. PBM can act as a preconditioning regimen and can interact with exercise on muscles.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/php.12864

Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation

The purpose of this study is to explore the possibilities for the application of laser therapy in medicine and dentistry by analyzing lasers' underlying mechanism of action on different cells, with a special focus on stem cells and mechanisms of repair. The interest in the application of laser therapy in medicine and dentistry has remarkably increased in the last decade. There are different types of lasers available and their usage is well defined by different parameters, such as: wavelength, energy density, power output, and duration of radiation. Laser irradiation can induce a photobiomodulatory (PBM) effect on cells and tissues, contributing to a directed modulation of cell behaviors, enhancing the processes of tissue repair. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), can induce cell proliferation and enhance stem cell differentiation. Laser therapy is a non-invasive method that contributes to pain relief and reduces inflammation, parallel to the enhanced healing and tissue repair processes. The application of these properties was employed and observed in the treatment of various diseases and conditions, such as diabetes, brain injury, spinal cord damage, dermatological conditions, oral irritation, and in different areas of dentistry.

Photobiomodulation-Underlying Mechanism and Clinical Applications.

Light-emitting diode photobiomodulation is the newest category of nonthermal light therapies to find its way to the dermatologic armamentarium. In this article, we briefly review the literature on the development of this technology, its evolution within esthetic and medical dermatology, and provide practical and technical considerations for use in various conditions. This article also focuses on the specific cell-signaling pathways involved and how the mechanisms at play can be put to use to treat a variety of cutaneous problems as a stand-alone application and/or complementary treatment modality or as one of the best photodynamic therapy light source.

Light-emitting diodes (LEDs) in dermatology.

In the last decade, it has been proposed that the sun's IR-A wavelengths might be deleterious to human skin and that sunscreens, in addition to their desired effect to protect against UV-B and UV-A, should also protect against IR-A (and perhaps even visible light). Several studies showed that NIR may damage skin collagen content via an increase inMMP-1 activity in the same manner as is known for UVR. Unfortunately, the artificial NIR light sources used in such studies were not representative of the solar irradiance. Yet, little has been said about the other side of the coin. This article will focus on key information suggesting that IR-A may be more beneficial than deleterious when the skin is exposed to the appropriate irradiance/dose of IR-A radiation similar to daily sun exposure received by people in real life.IR-A might even precondition the skin--a process called photo prevention--from an evolutionary standpoint since exposure to early morning IR-A wavelengths in sunlight may ready the skin for the coming mid-day deleterious UVR. Consequently IR-A appears to be the solution, not the problem. It does more good than bad for the skin. It is essentially a question of intensity and how we can learn from the sun. © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

pdf/infrared-and-skin-friend-or-foe-4qtswecwdx.pdf

Infrared and skin: Friend or foe.

https://www.jidonline.org/article/S0022-202X(15)34174-9/pdf

Regulation of skin collagen metabolism in vitro using a pulsed 660 nm LED light source: clinical correlation with a single-blinded study.

A photoactivation device for modulating the physiology of a target biological activity by directing a photoactivating light beam having predetermined parameters onto the target tissue. The device comprises a photoactivating light source, a positioning means operatively coupled to the light source allowing selective positioning of the light source relative to the target surface and a position evaluating means for determining the position of the light source relative to the target surface.

Method and device for the treatment of mammalian tissues

Background Jet injection can be defined as a needle-free drug delivery method in which a high-speed stream of fluid impacts the skin and delivers a drug. Despite 75 years of existence, it never reached its full potential as a strategic tool to deliver medications through the skin. Objective The aim of this review was to evaluate and summarize the evolution of jet injection intradermal drug delivery method including technological advancements and new indications for use. Methods A review of the literature was performed with no limits placed on publication date. Results Needleless injectors not only reduce pain during drug delivery but also confine the drug more evenly in the dermis. Understanding skin properties of the injection site is a key factor to obtain optimal results as well as setting the right parameters of the jet injector. Until the advent of disposable jet injectors/cartridges, autoclaving of the injector remains the only reliable method to eliminate the risk of infection. Needle-free intradermal injection using corticosteroids and/or local anesthetics is well documented with promising indications being developed. Limitations Limitations of the review include low-quality evidence, small sample sizes, varying treatment parameters, and publication bias. Conclusion New developments may help reconsider the use of jet injection technology. Future studies should focus on measurable optimized parameters to insure a safe and effective outcome.

/pdf/current-trends-in-needle-free-jet-injection-an-update-3vprsxeupv.pdf

Current trends in needle-free jet injection: an update.

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