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, a facile phototherapy molecule (SCy-Le) with the enhancement of non-radiative energy transfer is designed 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 (Δ E S1–T1 ), promotes electron system crossing, enhances capacity of reactive oxygen species generation, and causes a significant increase in temperature by improving vibrational relaxation. SCy-Le shows more than 99% bacterial killing rate against both methicillin-resistant Staphylococcus aureus and its biofilms in vitro and causes bacteria-induced wound healing in mice. This work will provide a new perspective for the design of phototherapy agents, and the emerging photochemotherapy will be a promising approach to combat the problem of antibiotic resistance.
Second near-infrared (NIR-II) window responsive phototheranostic agents have a precise spatiotemporal potential for the diagnosis and treatment of cancer. In this study, a full-spectrum responsive ZrO2-based phototheranostic agent was found to achieve NIR-II photoacoustic (PA) imaging-guided tumour-targeting phototherapy. Initially, the ZrO2-based phototheranostic agent was fabricated through NaBH4 reduction to form boron-doped oxygen-deficient zirconia (ZrO2−x-B), an amino-functionalised SiO2 shell and a further covalent connection with hyaluronic acid (HA), namely, ZrO2−x-B@SiO2-HA. In the ZrO2−x-B@SiO2-HA system, the oxygen vacancy and boron doping resulted in full-spectrum absorption, enabling a high NIR-II photothermal conversion, high-resolution PA imaging ability and a remarkable production of reactive oxygen species (ROS). The surface modification of HA provided ZrO2−x-B@SiO2-HA with water dispersibility and a targeting capability for CD44 overexpressed cancer cells. Furthermore, in vitro and in vivo experiments showed that NIR-II activated ZrO2−x-B@SiO2-HA had a targeted photothermal/photodynamic effect for cancer elimination under the real-time guidance of NIR-II PAs. Hence, ZrO2−x-B@SiO2-HA displays a precise NIR-II radiation-activated phototheranostic potential for PA imaging-guided cancer-targeting photothermal/photodynamic therapy.
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