Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.
Background: In medicine, lasers have been used predominantly for applications, which are broadly termed low level laser therapy (LLLT), phototherapy or photobiomodulation. This study aimed to establish cellular responses to Helium-Neon (632.8 nm) laser irradiation using different laser fluences (0.5, 2.5, 5, 10, and 16 J/cm 2 ) with a single exposure on 2 consecutive days on normal and wounded human skin fibroblasts. Materials and Methods: Changes in normal and wounded fibroblast cell morphology were evaluated by light microscopy. Changes following laser irradiation were evaluated by assessing the mitochondrial activity using adenosine triphosphate (ATP) luminescence, cell proliferation using neutral red and an alkaline phosphatase (ALP) activity assay, membrane integrity using lactate dehydrogenase (LDH), and percentage cytotoxicity and DNA damage using the Comet assay. Results: Morphologically, wounded cells exposed to 5 J/ cm 2 migrate rapidly across the wound margin indicating a stimulatory or positive influence of phototherapy. A dose of 5 J/cm 2 has a stimulatory influence on wounded fibroblasts with an increase in cell proliferation and cell viability without adversely increasing the amount of cellular and molecular damage. Higher doses (10 and 16 J/cm 2 ) were characterized by a decrease in cell viability and cell proliferation with a significant amount of damage to the cell membrane and DNA. Conclusions: Results show that 5 J/cm 2 stimulates mitochondrial activity, which leads to normalization of cell function and ultimately stimulates cell proliferation and migration of wounded fibroblasts to accelerate wound closure. Laser irradiation can modify cellular processes in a dose or fluence (J/cm 2 ) dependent manner. Lasers Surg.
The results show that the correct energy density or fluence (J/cm(2)) and number of exposures can stimulate cellular responses of wounded fibroblasts and promote cell migration and cell proliferation by stimulating mitochondrial activity and maintaining viability without causing additional stress or damage to the wounded cells. Results indicate that the cumulative effect of lower doses (2.5 or 5 J/cm(2)) determines the stimulatory effect, while multiple exposures at higher doses (16 J/cm(2)) result in an inhibitory effect with more damage.
The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.
This review article is based on specifically targeted nanoparticles that have been used
in the treatment of melanoma. According to the Skin Cancer Foundation, within 2017 an
estimated 9730 people will die due to invasive melanoma. Conventional treatments for
nonmalignant melanoma include surgery, chemotherapy, and radiation. For the treatment of
metastatic melanoma, 3 therapeutic agents have been approved by the Food and Drug
Administration: dacarbazine, recombinant interferon α-2b, and high-dose interleukin 2.
Photodynamic therapy is an alternative therapy that activates a photosensitizer at a
specific wavelength forming reactive oxygen species which in turn induces cell death; it
is noninvasive with far less side effects when compared to conventional treatments.
Nanoparticles are generally conjugated to photosynthetic drugs, since they are
biocompatible, stabile, and durable, as well as have a high loading capacity, which
improve either passive or active photosensitizer drug delivery to targeted cells.
Therefore, various photosynthetic drugs and nanoparticle drug delivery systems
specifically targeted for melanoma were analyzed in this review article in relation to
either their passive or their active cellular uptake mechanisms in order to deduce the
efficacy of photodynamic therapy treatment for metastatic melanoma which currently remains
ongoing. The overall findings from this review concluded that no current photodynamic
therapy studies have been performed in relation to active nanoparticle platform
photosensitizer drug carrier systems for the treatment of metastatic melanoma, and so this
type of research requires further investigation into developing a more efficient active
nano-photosensitizer carrier smart drug that can be conjugated to specific cell surface
receptors and combinative monoclonal antibodies so that a further enhanced and more
efficient form of targeted photodynamic therapy for the treatment of metastatic melanoma
can be established.
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