BODIPY dyes tend to be highly fluorescent, but their emissions can be attenuated by adding substituents with appropriate oxidation potentials. Substituents like these have electrons to feed into photoexcited BODIPYs, quenching their fluorescence, thereby generating relatively long-lived triplet states. Singlet oxygen is formed when these triplet states interact with 3O2. In tissues, this causes cell damage in regions that are illuminated, and this is the basis of photodynamic therapy (PDT). The PDT agents that are currently approved for clinical use do not feature BODIPYs, but there are many reasons to believe that this situation will change. This review summarizes the attributes of BODIPY dyes for PDT, and in some related areas.

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BODIPY dyes in photodynamic therapy.

Singlet molecular oxygen, 02(’Ag) , has been intensively investigated over the last few decades, primarily in relation to photosensitization reactions. In combination with the increasing awareness and interest in singlet oxygen has been the development of various methodologies for the detection and quantification of singlet oxygen production. A large body of literature now exists concerning the singlet oxygengenerating abilities of a large variety of endogenous and exogenous compounds that can be photoactivated in the UV and visible regions of the electromagnetic spectrum. The purpose of this review was to compile data from many different sources to provide a convenient resource for biological scientists with interest in this area. This compilation is essentially an updated subset of the excellent comprehensive review on singlet oxygen yields by Wilkinson et af. (l), which, unlike this compilation, was not limited to biological molecules. The data are current up to the early months of 1999. The following tables include various related parameters in addition to the central parameter of the quantum yield of singlet oxygen generation (QA) for a given photosensitizer. The methodology or technique used to measure the QA value for each entry is given and ranges from direct detection of the luminescence produced on relaxation of singlet oxygen (time-resolved [TRILIT or steady-state [SSIL]), calorimetric

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-1097.1999.tb08240.x

A Compilation of Singlet Oxygen Yields from Biologically Relevant Molecules

A gold nanorod (GNR)−photosensitizer complex was developed for noninvasive near-infrared fluorescence imaging and cancer therapy. We showed that (a) fluorescence emission and singlet oxygen generation by AlPcS4 were quenched after complex formation with GNRs; (b) 4-fold greater intracellular uptake and better in vitro phototoxicity were observed in GNR−AlPcS4-treated cells than in free AlPcS4-treated cells; and (c) after intravenous injection of the GNR−AlPcS4 complex, tumor sites were clearly identified on near-infrared fluorescence images as early as 1 h after injection. The tumor-to-background ratio increased over time and was 3.7 at 24 h; tumor growth reduced by 79% with photodynamic therapy (PDT) alone and by 95% with dual photothermal therapy (PTT) and PDT. This novel multifunctional nanomedicine may be useful for near-infrared fluorescence imaging and PTT/PDT in various cancers.

Gold nanorod-photosensitizer complex for near-infrared fluorescence imaging and photodynamic/photothermal therapy in vivo.

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.

https://www.mdpi.com/1996-1944/6/3/817/pdf

Dye Sensitizers for Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising new treatment modality for several diseases, most notably cancer. In PDT, light, O2, and a photosensitizing drug are combined to produce a selective therapeutic effect. Lately, there has been active research on new photosensitizer candidates, because the most commonly used porphyrin photosensitizers are far from ideal with respect to PDT. Finding a suitable photosensitizer is crucial in improving the efficacy of PDT. Recent synthetic activity has created such a great number of potential photosensitizers for PDT that it is difficult to decide which ones are suitable for which pathological conditions, such as various cancer species. To facilitate the choice of photosensitizer, this review presents a thorough survey of the photophysical and chemical properties of the developed tetrapyrrolic photosensitizers. Special attention is paid to the singlet-oxygen yield (ΦΔ) of each photosensitizer, because it is one of the most important photodynamic parameters in PDT. Also, in the survey, emphasis is placed on those photosensitizers that can easily be prepared by partial syntheses starting from the abundant natural precursors, protoheme and the chlorophylls. Such emphasis is justified by economical and environmental reasons. Several of the most promising photosensitizer candidates are chlorins or bacteriochlorins. Consequently, chlorophyll-related chlorins, whose ΦΔ have been determined, are discussed in detail as potential photosensitizers for PDT. Finally, PDT is briefly discussed as a treatment modality, including its clinical aspects, light sources, targeting of the photosensitizer, and opportunities.

Research advances in the use of tetrapyrrolic photosensitizers for photodynamic therapy.

The singlet oxygen quantum yield of photodynamic agents was measured at 546nm, 630 nm and on the far-red absorption peak. The technique employed is available in most laboratories, in which the photosensitization of lysozyme is used as an internal actinometer. Measurements in a pH 7.4 phosphate buffer plus 1% Triton X-100 (PB/X100) are scaled to 0.52 for methylene blue in the phosphate buffer. The average quantum yields are: hematoporphyrin IX (0.73), protoporphyrin IX (0.56), zinc protoporphyrin IX (0.91), mesotetra-(4-sulfonato-phenyl)porphine (0.61), PhotofrinR (0.89), benzoporphyrin derivative monoacid ring-A (0.84), chlorin e6 in PB (0.64), pheophorbide a (0.69), and aluminum phthalocyanine tetrasulfonate (0.38). Protection factors were measured for added azide ion, 1,4-diazabicyclo[2,2,2]-octane, and superoxide dismutase. Spectral evidence is presented for chlorin e6 interactions with PB/TX100 and for binding to lysozyme.

Jim M Fernandez

Papers

Singlet oxygen generation by photodynamic agents