Antimicrobial Photodynamic Therapy in Combating Pneumonia: Evaluating Strategies to Overcome the Pulmonary Surfactant Barrier

• Grant number: 25/04310-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Vanderlei Salvador Bagnato
• Grantee: Isabelle Almeida de Lima
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07276-1 - CEPOF - Optics and Photonic Research Center, AP.CEPID

Abstract

Pneumonia is one of the leading causes of death worldwide, a situation worsened by the rise of antimicrobial resistance. Antimicrobial Photodynamic Therapy (aPDT) has emerged as a promising alternative, as its mechanism is based on oxidative damage-induced bacterial death, presenting a low risk of resistance development. Our research group has been using indocyanine green (ICG) and external infrared illumination to control infections. Although effective **in vitro** against *Streptococcus pneumoniae*, its **in vivo** application faces challenges due to pulmonary surfactant (PS), which traps photosensitizer molecules and limits therapy efficiency. However, the combination of ICG with the Gantrez AN-139 copolymer has been shown to completely eradicate the bacterium **in vitro** (6.3 log¿¿), even in the presence of PS, and to achieve a reduction of approximately 3 log¿¿ in a murine model. Additionally, it has been demonstrated that aPDT can enhance the susceptibility of antibiotic-resistant microorganisms. To further improve **in vivo** aPDT efficacy, this project will conduct **in vitro** studies combining this therapy with antibiotics in the presence of PS, using both susceptible and resistant strains. By overcoming the PS barrier and optimizing the antimicrobial response, this study will strengthen the potential of aPDT, opening new perspectives for the effective treatment of respiratory infections, including resistant ones. (AU)