4.5 Article

Antibacterial Photodynamic Therapy in the Near-Infrared Region with a Targeting Antimicrobial Peptide Connected to a p-Extended Porphyrin

Journal

ACS INFECTIOUS DISEASES
Volume 8, Issue 8, Pages 1509-1520

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.2c00131

Keywords

antimicrobial photodynamic therapy; near infrared; porphyrin; antimicrobial peptide; bacteria; keratinocyte

Funding

  1. Ministry of Education and Research for a Ph.D. fellowship
  2. project SAFEST [ANR-21-CE18-0043]
  3. Italian CNR (project PHEEL) [ANR-21-CE18-0043]
  4. [GDR 2067 MAPYRO]
  5. Agence Nationale de la Recherche (ANR) [ANR-21-CE18-0043] Funding Source: Agence Nationale de la Recherche (ANR)

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The increase of antimicrobial resistance is a major health problem worldwide, and new bactericidal strategies are needed. Antimicrobial photodynamic therapy (a-PDT) can generate reactive oxygen species to target cellular structures, reducing the risk of bacterial resistance. A new conjugate consisting of an antimicrobial peptide and a pi-extended porphyrin photosensitizer has been designed to effectively kill both Gram-positive and Gram-negative bacteria when excited by near IR. Moreover, this conjugate can achieve a low minimum bactericidal concentration without causing toxicity to skin cells.
The increase of antimicrobial resistance to conventional antibiotics is worldwide a major health problem that requires the development of new bactericidal strategies. Antimicrobial photodynamic therapy (a-PDT) that generates reactive oxygen species acting on multiple cellular targets is unlikely to induce bacterial resistance. This localized treatment requires, for safe and efficient treatment of nonsuperficial infections, a targeting photosensitizer excited in the near IR. To this end, a new conjugate consisting of an antimicrobial peptide linked to a pi-extended porphyrin photosensitizer was designed for a PDT. Upon irradiation at 720 nm, the conjugate has shown at micromolar concentration strong bactericidal action on both Gram-positive and Gramnegative bacteria. Moreover, this conjugate allows one to reach a low minimum bactericidal concentration with near IR excitation without inducing toxicity to skin cells.

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