Second harmonic generation-mediated Photodynamic Therapy for Staphylococcus aureus: A novel approach using Bismuth Ferrite-Protoporphyrin IX conjugates

Photodynamic therapy (PDT) is a minimally invasive treatment modality that utilizes photosensitizing agents, light, and molecular oxygen to produce cytotoxic reactive oxygen species (ROS) to treat cancerous cells and bacterial infections. However, the effectiveness of PDT is often limited by the penetration depth of the light used to activate the photosensitizer (PS). We propose an effective method to address this challenge using Second Harmonic Generation (SHG), a nonlinear optical process in which two identical photons combine to form a new photon with double the frequency. This technique enables the utilization of longer wavelengths for enhanced tissue penetration, subsequently converting them into shorter wavelengths that align with the absorption characteristics of the photosensitizer. Thus, to achieve a highly effective production of SHG, we successfully synthesized the Harmonic Nanoparticle (HNP), Bismuth Ferrite (BFO). Subsequently, BFO was conjugated with Protoporphyrin IX (PPIX) to get BFO-PPIX conjugates for PDT treatment. These were exposed to Near Infrared (NIR) femtoseconds pulsed laser with a wavelength of 798 nm. PDT experiments using BFO-PPIX conjugates and an 8-minute irradiation by a 798 nm pulse laser reduced the survival rate of cultured Staphylococcus aureus (S. aureus) bacterial cells to 44.5 % ± 3.4 %. To the best of our knowledge, BFO and BFO-PPIX conjugates have not been used previously for advancing the conventional PDT treatment using SHG for deeper and precise treatment in S. aureus.