Triphenylamine-Substituted Nile Red Derivatives with Efficient Reactive Oxygen Species Generation for Robust and Broad-Spectrum Antimicrobial Photodynamic Therapy and Abscess Wound Healing

Abstract

Infections caused by drug-resistant bacteria represent a major contributor to high mortality rates, underscoring the urgent need for effective non-antibiotic drugs and alternative therapies. Antimicrobial photodynamic therapy (aPDT) emerges as an innovative treatment due to its minimal drug resistance. Herein, a series of Nile Red derivatives is synthesized by a donor engineering strategy. Notably, NTPA featuring triphenylamine (TPA) as the electron-donating group, exhibited the highest production of reactive oxygen species (ROS). The enhanced electron donating-accepting (D-A) property effectively reduced the energy gap between S₁ and T₁ (ΔE_S-T), facilitating intersystem crossing (ISC) with a larger spin-orbit coupling (SOC) constant. Furthermore, the twisted conformation profoundly suppressed the quenching of ROS. As expected, an over 470-fold increase in ROS production is observed, predominantly comprising type-I ROS. NTPA nanoparticles (NPs) exhibited exceptional in vitro killing ability against various drug-resistant bacteria, with inhibition efficiency even reaching 99.9%. In the methicillin-resistant staphylococcus aureus (MRSA)-induced abscess model, NTPA NPs facilitated complete wound healing within just 8 days following a single administration and irradiation, highlighting their exceptional bactericidal and wound-healing promotion capabilities. Overall, this work inspired the construction of efficient Nile Red-based type-I photosensitizers (PSs) and the development of a new broad-spectrum aPDT method for drug-resistant bacteria treatment.