Lung surfactant negatively affects the photodynamic inactivation of bacteria-in vitro and molecular dynamic simulation analyses

Author(s)

Kassab, Giulia ; Diaz Tovar, Johan Sebastian ; Pereira Souza, Lucas Miguel ; Magalhaes Costa, Rayla Kelly ; Silva, Rudielson Santos ; Pimentel, Andre Silva ; Kurachi, Cristina ; Bagnato, Vanderlei Salvador

• Document type: Journal article
• Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 119, n. 25, p. 9-pg., 2022-06-21.

Abstract

In the context of the rapid increase of antibiotic-resistant infections, in particular of pneumonia, antimicrobial photodynamic therapy (aPDT), the microbiological application of photodynamic therapy (PDT), comes in as a promising treatment alternative since the induced damage and resultant death are not dependent on a specific biomolecule or cellular pathway. The applicability of aPDT using the photosensitizer indocyanine green with infrared light has been successfully demonstrated for different bacterial agents in vitro, and the combination of pulmonary delivery using nebulization and external light activation has been shown to be feasible. However, there has been little progress in obtaining sufficient in vivo efficacy results. This study reports the lung surfactant as a significant suppressor of aPDT in the lungs. In vitro, the clinical surfactant Survanta (R) reduced the aPDT effect of indocyanine green, Photodithazine (R), bacteriochlorintrizma, and protoporphyrin IX against Streptococcus pneumoniae. The absorbance and fluorescence spectra, as well as the photobleaching profile, suggested that the decrease in efficacy is not a result of singlet oxygen quenching, while a molecular dynamics simulation showed an affinity for the polar head groups of the surfactant phospholipids that likely impacts uptake of the photosensitizers by the bacteria. Methylene blue is the exception, likely because its high water solubility confers a higher mobility when interacting with the surfactant layer. We propose that the interaction between lung surfactant and photosensitizer must be taken into account when developing pulmonary aPDT protocols. (AU)

• FAPESP's process: 18/18188-0 - Photodynamic inactivation of Bacterial Pneumonia with nebulization of the photosensitizer and extracorporeal illumination
• Grantee: Giulia Kassab
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/50857-8 - National Institute in Basic Optics and Applied to Life Sciences
• Grantee: Vanderlei Salvador Bagnato
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/07276-1 - CEPOF - Optics and Photonic Research Center
• Grantee: Vanderlei Salvador Bagnato
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/50983-3 - INCT 2014: complex fluids
• Grantee: Antonio Martins Figueiredo Neto
• Support Opportunities: Research Projects - Thematic Grants