Photodynamic therapy (PDT) is a light triggered therapy by producing reactive oxygen species (ROS), but traditional PDT may suffer from the real‐time illumination that reduces the compliance of treatment and cause phototoxicity. A supramolecular photoactive G‐quartet based material is reported, which is self‐assembled from guanosine (G) and 4‐formylphenylboronic acid/1,8‐diaminooctane, with incorporation of riboflavin as a photocatalyst to the G4 nanowire, for post‐irradiation photodynamic antibacterial therapy. The G4‐materials, which exhibit hydrogel‐like properties, provide a scaffold for loading riboflavin, and the reductant guanosine for the riboflavin for phototriggered production of the therapeutic H2O2. The photocatalytic activity shows great tolerance against room temperature storage and heating/cooling treatments. The riboflavin‐loaded G4 hydrogels, after photo‐irradiation, are capable of killing gram‐positive bacteria (e.g., Staphylococcus aureus), gram‐negative bacteria (e.g., Escherichia coli), and multidrug resistant bacteria (methicillin‐resistant Staphylococcus aureus) with sterilization ratio over 99.999%. The post‐irradiated hydrogels also exhibit great antibacterial activity in the infected wound of the rats, revealing the potential of this novel concept in the light therapy.

Traditional photodynamic therapy (PDT) is dependent on externally applied light and oxygen, and the depth of penetration of these factors can be insufficient for the treatment of deep infections. The short half‐life and short diffusion distance of reactive oxygen species (ROS) also limit the antibacterial efficiency of PDT. Herein, we designed a targeting singlet oxygen delivery system, CARG‐Py, for irradiation‐free and oxygen‐free PDT. This system was converted to the “singlet oxygen battery” CARG‐1O2 and released singlet oxygen without external irradiation or oxygen. CARG‐1O2 is composed of pyridones coupled to a targeting peptide that improves the utilization of singlet oxygen in deep multidrug‐resistant bacterial infections. CARG‐1O2 was shown to damage DNA, protein, and membranes by increasing the level of reactive oxygen inside bacteria; the attacking of multiple biomolecular sites caused the death of methicillin‐resistant Staphylococcus aureus (MRSA). An in vivo study in a MRSA‐infected mouse model of pneumonia demonstrated the potential of CARG‐1O2 for the efficient treatment of deep infections. This work provides a new strategy to improve traditional PDT for irradiation‐ and oxygen‐free treatment of deep infections while improving convenience of PDT.

Traditional photodynamic therapy (PDT) is dependent on externally applied light and oxygen, and the depth of penetration of these factors can be insufficient for the treatment of deep infections. The short half‐life and short diffusion distance of reactive oxygen species (ROS) also limit the antibacterial efficiency of PDT. Herein, we designed a targeting singlet oxygen delivery system, CARG‐Py, for irradiation‐free and oxygen‐free PDT. This system was converted to the “singlet oxygen battery” CARG‐1O2 and released singlet oxygen without external irradiation or oxygen. CARG‐1O2 is composed of pyridones coupled to a targeting peptide that improves the utilization of singlet oxygen in deep multidrug‐resistant bacterial infections. CARG‐1O2 was shown to damage DNA, protein, and membranes by increasing the level of reactive oxygen inside bacteria; the attacking of multiple biomolecular sites caused the death of methicillin‐resistant Staphylococcus aureus (MRSA). An in vivo study in a MRSA‐infected mouse model of pneumonia demonstrated the potential of CARG‐1O2 for the efficient treatment of deep infections. This work provides a new strategy to improve traditional PDT for irradiation‐ and oxygen‐free treatment of deep infections while improving convenience of PDT.