Artificial and natural photosensitizers in photodynamic therapy: expanded porphycene conjugates and hypericin


Hally García, Cormac Elias   


This thesis reports the study of antimicrobial and antineoplastic applications of novel 2-aminothiazolo porphycene conjugates and Hypericin in Photodynamic therapy (PDT), while aiming to understand their mechanism of action. The conjugation of 9-isothiocyanate-2,7,12,17-methoxyethylporphycene to two hydrophilic entities, gentamicin as an antibiotic and triphenylphosphonium as a lipophilic cation, rendered amphiphilic compounds with high biological activity against microorganisms and HeLa cells. The conjugates presented dual aromatic systems, highly absorbing in the deep red with high singlet oxygen yields. Their fluorescence, despite being dim, was still exploited in applications such as confocal microscopy and even stimulated emission depletion super-resolution microscopy (STED). The Gentamicin conjugate was able to inactivate S. aureus, E. coli and C. albicans in the submicromolar range, but lacking the intended selectivity since it also inactivates cancer cells. The conjugate endowed with the Triphenylphosphonium cation presented less activity against microorganisms than the previous conjugate, but higher for cancer PDT due to the partial subcellular localization guidance towards mitochondria. Hypericin, on the other hand, is a powerful and well-known naturally occurring photosensitizer which is costly to both purify from a plant extract or chemically synthesized. In this regard, a non-purified lyophilized hydroalcoholic H. perforatum extract was compared with pure hypericin, observing how its photophysical properties are not quenched by other compounds in the extract and that its antimicrobial activity against S. aureus was preserved. Continuing with Hypericin, retinoic acid was incorporated into the previously reported β-lactoglobulin-Hypericin complex in order to test its antimicrobial in vitro potential. Despite being a singlet oxygen quencher, this addition did not affect the Hypericin’s performance against S. aureus, proving its potential as a double payload vehicle when treating acne vulgaris: Hypericin to treat infections and the retinoid to calm inflammation.




Nonell Marrugat, Santiago 
Viappiani, Cristiano  


IQS SE - Química Analítica i Aplicada

Date of defense