The synthesis and photophysical characteristics of a pH responsive near-infrared fluorescence imaging probe is described. A key feature is the ability to conjugate the probe by an alkyne-azide cycloaddition reaction and its reversible response of fluorescence intensity across the physiological pH range.
BACKGROUND: Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF 2 -chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06. METHODS: A multi-modality imaging approach was employed to assess efficacy of treatment, as well as probe the mechanism of action of ADPM06-mediated PDT. RESULTS: Tumour ablation in 71% of animals bearing mammary tumours was achieved after delivery of 2 mg kg À1 of ADPM06 followed immediately by light irradiation with 150 J cm À2 . The inherent fluorescence of ADPM06 was utilised to monitor organ biodistribution patterns, with fluorescence reaching baseline levels in all organs within 24 h. Mechanism of action studies were carried out using dynamic positron emission tomography and magnetic resonance imaging techniques, which, when taken together, indicated a decrease in tumour vascular perfusion and concomitant reduction in tumour metabolism over time after treatment. CONCLUSION: The encouraging treatment responses in vivo and vascular-targeting mechanism of action continue to indicate therapeutic benefit for this new class of photosensitiser.
Herein we describe a new antimicrobial photodynamic therapeutic (PDT) agent based upon the brominated BF(2) chelated tetraarylazadipyrromethene photosensitizer class. Bis-ammonium salt substitution of the photosensitizer promoted a rapid 10 min uptake into Gram-positive and -negative bacterial strains and pathogenic yeasts. A photosensitizer and light dose response analysis for methicillin-sensitive S. aureus showed an impressive antibacterial efficacy with 1, 2, and 5 μg/mL 6. Specifically, light activation with a dose of 16 J/cm(2) and 5 μg/mL 6 resulted in a 6.8 and 3.4 log(10) reduction of S. aureus and a clinically defined methicillin-resistant Staphylococcus aureus (MRSA) strain, respectively. Encouragingly, a broad spectrum pathogen response (using 5 μg/mL 6 and 75 J/cm(2)) was observed with 3.6 and 5.7 log(10) decreases in viable cell numbers achievable for Gram-negative bacterium E. coli and the pathogenic yeast C. albicans, respectively. The photophysical and cell eradicating characteristics of this bis-cationic PDT agent suggest that it has broad potential in antimicrobial therapeutics.
Substoichiometric loadings of DBU catalyse the efficient 1,4-addition of alcohols and non-nucleophilic amines such as pyrrole to activated alkenes; the application of this methodology in a one-pot synthesis of a natural product, and as a novel strategy for the synthesis of mono-protected 1,3-carbonyl compounds is reported.
Strategic incorporation of sulfonic acid, carboxylic acid or ammonium salt motifs generate water soluble BF(2)-chelated tetraarylazadipyrromethenes which exhibit strong near infra-red (NIR) emissions above 720 nm and can be readily imaged in both eukaryotic and prokaryotic cells.
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