Tailored Phototherapy Agent by Infection Site in Situ Activated against Methicillin-Resistant S. aureus.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a promising treatment approach for multidrug resistant infections. PDT/PTT combination therapy can more efficiently eliminate pathogens without drug resistance. The key to improve the efficacy of photochemotherapy is the utilization efficiency of non-radiation energy of phototherapy agents. Herein, we design a facile phototherapy molecule (SCy-Le) with the enhancement of non-radiative energy transfer by an acid stimulation under a single laser. Introduction of the protonated receptor into SCy-Le results in a distorted intramolecular charge in the infected acidic microenvironment, pH≈5.5, which in turn enhances light capture, reduces the singlet-triplet transition energies (ΔE S1-T1 ), promotes electron system crossing, enhances capacity of ROS generation, and a significant increase in temperature by improving vibrational relaxation. SCy-Le showed more than 99% bacterial killing rate against both methicillin-resistant Staphylococcus aureus (MRSA) and its biofilms in vitro, and caused bacteria-induced wound healing in mice. This work will provide a new perspective for the design of phototherapy agents, and the emerging photochemotherapy will a promising approach to combat the problem of antibiotic resistance. This article is protected by copyright. All rights reserved.