No abstract

Purpose of Review-The goal of this review is to summarize the field to date and to discuss strengths and limitations of low-level laser (light) therapy (LLLT) for the future investigation as a treatment of inflammatory disease. Recent Findings-LLLT is a promising therapeutic, particularly for those diseases of skin and joints because they are most accessible to treatment. Indeed, the known mechanisms of LLLT support its use for anti-inflammatory purposes, as well as stimulation of tissue growth and repair. Although the standard of care for the majority of inflammatory diseases is immunosuppressive agents such as corticosteroids with undesirable toxicities, LLLT offers a unique approach by being non-invasive and incurring minimal side effects. It is also relatively inexpensive and accessible and even has the possibility to be patient directed at home. Summary-There is evidence that LLLT is able to modulate the immune system at the skin and joint, and it has been shown to be efficacious in humans by affecting bacterial colonization as it may pertain to chronic rhinosinusitis. However, there is variability in the methods of laser application as well as a lack of evidence for laser type, dose-ranging studies, and wavelength selection that create barriers to the implementation of LLLT without further more rigorous and standardized study. The heterogeneity makes it difficult to draw strong conclusions about the efficacy of LLLT and its mechanisms.

Two new compounds, including a para-benzoquinone ring-containing abietane (1), a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16), were isolated from an extract prepared from the cones of Taxodium distichum, collected in central Ohio. The active subfraction from which all compounds isolated in this study were purified was tested in vivo using Leishmania donovani-infected mice, and was found to dose-dependently reduce the parasite burden in the murine livers after iv administration of this crude mixture at 5.6 and 11.1 mg/kg. The structures of 1 and 2 were established by detailed 1D- and 2D-NMR experiments, HRESIMS data, and electronic circular dichroism studies. Compounds 3 and 4 were each fully characterized spectroscopically and also isolated from a natural source for the first time. Compounds 2-16 were tested in vitro against L. donovani promastigotes and L. amazonensis intracellular amastigotes. Compound 2 was the most active against L. amazonensis amastigotes (IC50 = 1.4 μM), and 10 was the most potent against L. donovani promastigotes (IC50 = 1.6 μM). These compounds may be suggested for further studies such as in vivo experimentation either alone or in combination with other Taxodium isolates.

Herein, the use of red blood cells (RBCs) as carriers of cytoplasmically interned phototherapeutic agents is described. Photolysis promotes drug release from the RBC carrier thereby providing the means to target specific diseased sites. This strategy is realized with a vitamin B12‐taxane conjugate (B12‐TAX), in which the drug is linked to the vitamin via a photolabile CoC bond. The conjugate is introduced into mouse RBCs (mRBCs) via a pore‐forming/pore‐resealing procedure and is cytoplasmically retained due to the membrane impermeability of B12. Photolysis separates the taxane from the B12 cytoplasmic anchor, enabling the drug to exit the RBC carrier. A covalently appended Cy5 antenna sensitizes the conjugate (Cy5‐B12‐TAX) to far red light, thereby circumventing the intense light absorbing properties of hemoglobin (350–600 nm). Microscopy and imaging flow cytometry reveal that Cy5‐B12‐TAX‐loaded mRBCs act as drug carriers. Furthermore, intravital imaging of mice furnish a real time assessment of circulating phototherapeutic‐loaded mRBCs as well as evidence of the targeted photorelease of the taxane upon photolysis. Histopathology confirms that drug release occurs in a well resolved spatiotemporal fashion. Finally, acoustic angiography is employed to assess the consequences of taxane release at the tumor site in Nu/Nu‐tumor‐bearing mice.

Arthritis is a leading cause of disability in adults, which can be intensely incapacitating. The location and intensity of the pain is both subjective and challenging to manage. Consequently, patient-directed delivery of anti-inflammatories is an essential component of future therapeutic strategies for the management of this disorder. The design and application of a light-responsive red blood cell (RBC)-conveyed dexamethasone (Dex) construct that enables targeted drug delivery upon illumination of the inflamed site is described. The red wavelength (650 nm) responsive nature of the phototherapeutic is validated using tissue phantoms mimicking the light absorbing properties of various skin types. Furthermore, photoreleased Dex has the same impact on cellular responses as conventional Dex. Murine RBCs containing the photoactivatable therapeutic display comparable circulation properties as fluorescently labeled RBCs. In addition, a single dose of light-targeted Dex delivery is fivefold more effective in suppressing inflammation than the parent drug, delivered serially over multiple days. These results are consistent with the notion that the circulatory system be used as an on-command drug depot, providing the means to therapeutically target diseased sites both efficiently and effectively.