Abstract
Photofrin® was first approved in the 1990s as a sensitizer for use in treating cancer via photodynamic therapy (PDT). Since then a wide variety of dye sensitizers have been developed and a few have been approved for PDT treatment of skin and organ cancers and skin diseases such as acne vulgaris. Porphyrinoid derivatives and precursors have been the most successful in producing requisite singlet oxygen, with Photofrin® still remaining the most efficient sensitizer (quantum yield = 0.89) and having broad food and drug administration (FDA) approval for treatment of multiple cancer types. Other porphyrinoid compounds that have received approval from US FDA and regulatory authorities in other countries include benzoporphyrin derivative monoacid ring A (BPD-MA), meta-tetra(hydroxyphenyl)chlorin (m-THPC), N-aspartyl chlorin e6 (NPe6), and precursors to endogenous protoporphyrin IX (PpIX): 1,5-aminolevulinic acid (ALA), methyl aminolevulinate (MAL), hexaminolevulinate (HAL). Although no non-porphyrin sensitizer has been approved for PDT applications, a small number of anthraquinone, phenothiazine, xanthene, cyanine, and curcuminoid sensitizers are under consideration and some are being evaluated in clinical trials. This review focuses on the nature of PDT, dye sensitizers that have been approved for use in PDT, and compounds that have entered or completed clinical trials as PDT sensitizers.
Highlights
In the medical arena, the treatment of skin diseases with the aid of light has been performed since1400 BC [1], and this technology is known as phototherapy
For photodynamic therapy (PDT) using Photofrin® as the photosensitizer, an argon pumped dye laser coupled to an optical fiber is used and it operates at 630 nm
Endogenous Protoporphyrin IX (PpIX, 7) induced by exogenous 1,5-aminolevulinic acid (ALA or Levulan Kerasticks®, 8) was US food and drug administration (FDA) approved for non-oncological PDT treatment of actinic keratosis in 1999 [36]
Summary
The treatment of skin diseases with the aid of light has been performed since. When a photosensitizer is not used, phototherapy is mainly employed in dermatology to treat vitamin D deficiency, neonatal jaundice, psoriasis, eczema, vitiligo, polymorphous light eruption, cutaneous T-cell lymphoma, lichen planus, and even to ease the symptoms of Parkinson’s disease [2,3,4]. Treatments involve psoriasis, atopic dermatitis, seborrheic dermatitis, eczema, alopecia areata, chronic cutaneous graft-versus-host disease, HIV-associated dermatoses, histiocytosis, lichen planus, mycosis fungoids, polymorphous light eruption, pityriasis lichenoides, lymphamatoid papulosis, prurigo, palmar and plantar pustulosis, and vitiligo [6]. Suitable dye sensitizers for PDT are mainly porphyrinoid compounds, including chlorins, bacteriochlorins, phthalocyanines, and related structures [9]. These compounds have extended conjugation and absorb light in the visible region, which makes them colored compounds or dyes.
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