Self-aggregation of the proteolytic forms of Verteporfin: An in silico and in vitro study

Author(s)

Calori, Italo Rodrigo ; Braga, Gustavo ; Tessaro, Andre Luiz ; Caetano, Wilker ; Tedesco, Antonio Claudio ; Hioka, Noboru

• Document type: Journal article
• Source: JOURNAL OF MOLECULAR LIQUIDS; v. 352, p. 9-pg., 2022-02-14.

Abstract

Verteporfin is a benzoporphyrin derivative monoacid ring A that has been historically and successfully used as a photosensitizer in clinical applications and in clinical trials including for cancer phototherapy. However, the photo-efficiency of Verteporfin is limited by self-aggregation in water, in which the various proteolytic forms present distinct self-aggregation tendencies. In this work, spectroscopic and computational studies were used to elucidate the self-aggregation behavior of the three proteolytic forms of Verteporfin. Additionally, the intracellular self-aggregation of Verteporfin was evaluated in U87MG cells line, a type of brain cancer considered incurable. The results indicated that the self-aggregation of Verteporfin in water is most likely modulated by formal charge effects following the order: neutral > m onoanionic > dicationic. UV-vis electronic spectroscopy and computational dynamics analyses suggested that J-type aggregates were primarily formed. Time-resolved fluorescence and fluorescence lifetime imaging microscopy (FLIM) confirmed that although such aggregates exist in solution and inside cells, there is no evidence of preferential self-aggregation in acidic organelles, such as lysosomes. The present approach allows a better understanding of the self-aggregation of other photosensitizers, particularly the influence of different proteolytic forms and organelles on the self-aggregation of compounds that can be protonated, and the heterogeneity of photosensitizers within intracellular compartments. (c) 2022 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 20/04507-6 - HYDROGENLS CONFINED IN 3D PRINTED MATRIX TO CONTROLLED AND SITE-SPECIFIC DELIVERY OF INGENOL-3-DODECANOATE AND FLUOROCHROME FOR PHOTODIAGNOSTIC AND THERAPY OF CEREBRAL TUMORS
• Grantee: Italo Rodrigo Calori
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/50181-1 - Use of drugs containing nanocarriers with photosensitizers and/or other active compounds applied to cell therapy and treatment of central nervous system disorders
• Grantee: Antonio Claudio Tedesco
• Support Opportunities: Research Projects - Thematic Grants