Safety and delivery efficiency of a photodynamic treatment of the lungs using indocyanine green and extracorporeal near infrared illumination

Abstract

Photodynamic inactivation (PDI) is a promising alternative for combating infections caused by antimicrobial resistant bacteria. Pneumonias are among the most worrisome infections because of their high-mortality rate. Previous studies have demonstrated the feasibility of using PDI with extracorporeal light to treat pneumonia. In this study, we analyzed key parameters for the viability of this treatment, including the selectivity of the photodynamic response for pathogens over host cells. Our results showed that PDI can induce killing of Staphylococcus aureus (of up to 4.18 log for the strain Xen29 and 3.62 log for Xen36) under conditions where little or no toxicity for host cells is observed. We validated pulmonary delivery of the photosensitizer and light in mice, using photobleaching as an indicator, and demonstrated preservation of healthy tissues as evidence of the safety of the protocol. Overall, PDI displays low toxicity on host tissues, making it a promising tool for treatment of pneumonias caused by S. aureus and other important pathogens.

Photodynamic inactivation ofStreptococcus pneumoniaewith external illumination at 808 nm through the ex vivo porcine thoracic cage

“…Specifically, it was shown conditions in which ICG is deposited in the respiratory tract and activated with extracorporeal light without causing acute lung or liver damage. A follow-up study also showed that there is no evidence of the toxicity of the aPDT protocol in mammalian cell lines and mice in conditions that would completely inactivate bacteria [39].…”

“…Recently, an additional study demonstrated the selective of a PDI treatment using ICG and infrared light at 808 nm in vitro and the safety of aPDT in a murine model [28].…”

Pulmonary antimicrobial photodynamic therapy and the role of the lung surfactant

“…Experiment performed in triplicate on 3 different occasions (n = 9), mean value and standard deviation are shown. Source: KASSAB et al 92 The effect of different concentrations of ICG on a variety of bacterial strains and mammalian cell lines is shown in Figure 7. The presence of ICG is able to hinder the growth of S. aureus starting from 12.5 µM, decreasing the final CFU count in about 3 logs for Xen29.…”

“…Experiment performed in triplicate on 3 different occasions (n = 9), mean value and standard deviation are shown. Source: KASSAB et al 92 Exposure to 808 nm infrared light alone did not cause death or inhibition to S. aureus strains nor to the lung cells lines (Figure 8). There was no statistically significant difference between groups for the bacteria.…”

“…In the stomach and liver, the increase in fluorescence was only statistically significant for the endotracheal group. Source: KASSAB et al 92 Irradiation using the 808-nm light device successfully reduced the fluorescence of ICG in the upper body of the mice (Figure 10). After the end of the nebulization (t=0 min), the fluorescence detected in the thorax of the animals that only received ICG continued to increase.…”