Universal “Three-in-One” Matrix to Maximize Reactive Oxygen Species Generation from Food and Drug Administration-Approved Photosensitizers for Photodynamic Inactivation of Biofilms

Biofilms, an accumulation of microorganisms, cause persistent bacterial infection and low cure rate due to the remarkable drug resistance. Photodynamic inactivation (PDI) is a promising treatment modality for bacterial infections, but the formation of biofilms raises new challenges for photosensitizers (PSs), particularly the reactive oxygen species (ROS) generation efficiency. Herein, through targeting the Jablonski energy diagram, we proposed a universal “three-in-one” matrix of Gd3+-ADP assembly for encapsulation and fixing of PSs to inhibit non-radiative transitions and promoting intersystem crossing (ISC) by the heavy atom and paramagnetic effects of Gd3+, eventually resulted in boosted ROS generation from the existing PSs (1.5–9.0-fold). Particularly, photophysical studies indicated that the matrix resulted in simultaneous ISC promotion and triplet-state lifetime lengthening, which is essential for ROS boosting. The PDI performance of the matrix was confirmed through fast and effective elimination of bacterial biofilms in 10–30 min. Moreover, successful therapy of a Pseudomonas aeruginosa biofilm-infected all-thickness third-degree burn wound was achieved within 11 days with Ce 6@CNs (matrix) but not feasible for matrix-free PSs (Ce 6 only), which highlighted the role of “three-in-one” matrix in ROS boosting.