Reusable and near-infrared light-activated Zinc(II) metalated porphyrin with synergetic PDT/PTT for eradicating bacterial pneumonia

Phototherapy is an alternative treatment for combating bacterial infections without inducing antibiotic resistance. We synthesized a reusable and NIR-responsive zinc-metalated porphyrin (DEP-BH) by designing a steady acceptor–donor-acceptor structure and expanding the π-conjugated system with zinc coordination. Compared with traditional photosensitizers, DEP-BH exhibited remarkable and stable photodynamic and photothermal therapy properties under NIR irradiation. Owing to the hydrophobicity of porphyrin, DEP-BHs were loaded into positively charged thermosensitive liposomes. When applied on Pseudomonas aeruginosa-induced stubborn pneumonia in vivo, NIR irradiating DEP-BH@TSLs nearly treated the pneumonia caused by the biofilm and down-regulated the lung inflammatory response after the administration of 0.04 μmol (0.28 mM for 3 times). Because of the photostability of DEP-BH, one nanotherapeutic dose can be repeated for two light treatments without multiple dosing, avoiding the wastage of resources and the operation complexity. Importantly, DEP-BH is expected to be the next generation of photosensitizers with high efficiency, representing a novel direction for the application of porphyrins.