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      Daylight-PDT: everything under the sun

      review-article
      , ,
      Biochemical Society Transactions
      Portland Press Ltd.
      ALA, cancer, daylight, PDT, skin, sun

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          Abstract

          5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) was first implemented over three decades ago and has since been mainly part of clinical practice for the management of pre-cancerous and cancerous skin lesions. Photodynamic therapy relies on the combination of a photosensitizer, light and oxygen to cause photo-oxidative damage of cellular components. 5-Aminolevulinic acid (ALA) is a natural precursor of the heme biosynthetic pathway, which when exogenously administered leads to the accumulation of the photoactivatable protoporphyrin IX. Although, effective and providing excellent cosmetic outcomes, its use has been restricted by the burning, stinging, and prickling sensation associated with treatment, as well as cutaneous adverse reactions that may be induced. Despite intense research in the realm of drug delivery, pain moderation, and light delivery, a novel protocol design using sunlight has led to some of the best results in terms of treatment response and patient satisfaction. Daylight PDT is the protocol of choice for the management of treatment of multiple or confluent actinic keratoses (AK) skin lesions. This review aims to revisit the photophysical, physicochemical and biological characteristics of ALA-PDT, and the underlying mechanisms resulting in daylight PDT efficiency and limitations.

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          Most cited references70

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          New photosensitizers for photodynamic therapy.

          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.
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            Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods

            Penetration depth of ultraviolet, visible light and infrared radiation in biological tissue has not previously been adequately measured. Risk assessment of typical intense pulsed light and laser intensities, spectral characteristics and the subsequent chemical, physiological and psychological effects of such outputs on vital organs as consequence of inappropriate output use are examined. This technical note focuses on wavelength, illumination geometry and skin tone and their effect on the energy density (fluence) distribution within tissue. Monte Carlo modelling is one of the most widely used stochastic methods for the modelling of light transport in turbid biological media such as human skin. Using custom Monte Carlo simulation software of a multi-layered skin model, fluence distributions are produced for various non-ionising radiation combinations. Fluence distributions were analysed using Matlab mathematical software. Penetration depth increases with increasing wavelength with a maximum penetration depth of 5378 μm calculated. The calculations show that a 10-mm beam width produces a fluence level at target depths of 1–3 mm equal to 73–88% (depending on depth) of the fluence level at the same depths produced by an infinitely wide beam of equal incident fluence. Meaning little additional penetration is achieved with larger spot sizes. Fluence distribution within tissue and thus the treatment efficacy depends upon the illumination geometry and wavelength. To optimise therapeutic techniques, light-tissue interactions must be thoroughly understood and can be greatly supported by the use of mathematical modelling techniques.
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              European guidelines for topical photodynamic therapy part 1: treatment delivery and current indications - actinic keratoses, Bowen's disease, basal cell carcinoma.

              Topical photodynamic therapy (PDT) is a widely used non-invasive treatment for certain non-melanoma skin cancers, permitting treatment of large and multiple lesions with excellent cosmesis. High efficacy is demonstrated for PDT using standardized protocols in non-hyperkeratotic actinic keratoses, Bowen's disease, superficial basal cell carcinomas (BCC) and in certain thin nodular BCC, with superiority of cosmetic outcome over conventional therapies. Recurrence rates following PDT are typically equivalent to existing therapies, although higher than surgery for nodular BCC. PDT is not recommended for invasive squamous cell carcinoma. Treatment is generally well tolerated, but tingling discomfort or pain is common during PDT. New studies identify patients most likely to experience discomfort and permit earlier adoption of pain-minimization strategies. Reduced discomfort has been observed with novel protocols including shorter photosensitizer application times and in daylight PDT for actinic keratoses.
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                Author and article information

                Journal
                Biochem Soc Trans
                Biochem Soc Trans
                BST
                Biochemical Society Transactions
                Portland Press Ltd.
                0300-5127
                1470-8752
                29 April 2022
                6 April 2022
                : 50
                : 2
                : 975-985
                Affiliations
                [1 ]Medicines Design, Department of Pharmacy and Pharmacology, University of Bath, Bath, U.K.
                [2 ]Medicines Development, Centre for Therapeutic Innovation, University of Bath, Bath, U.K.
                Author notes
                Correspondence: Charareh Pourzand ( prscap@ 123456bath.ac.uk )
                Author information
                http://orcid.org/0000-0002-9046-1155
                Article
                BST-50-975
                10.1042/BST20200822
                9162453
                35385082
                703cf87c-8d55-4301-ba7b-88d6264a8aa2
                © 2022 The Author(s)

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). Open access for this article was enabled by the participation of University of Bath in an all-inclusive Read & Publish agreement with Portland Press and the Biochemical Society under a transformative agreement with JISC.

                History
                : 8 December 2021
                : 28 February 2022
                : 11 March 2022
                Categories
                Cancer
                Therapeutics & Molecular Medicine
                Review Articles

                Biochemistry
                ala,cancer,daylight,pdt,skin,sun
                Biochemistry
                ala, cancer, daylight, pdt, skin, sun

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