Spatial multiple distortion as a facile strategy boosting the efficacy of photothermal and photodynamic therapy.

Phototherapy, distinguished by its exceptional selectivity, noninvasive nature, and negligible drug resistance, has emerged as a promising antibiotic-free antimicrobial approach. However, the therapeutic efficacy of organic photosensitizers (PSs), particularly porphyrin-based systems, is significantly limited by strong π-π stacking-induced self-aggregation, an inherent challenge arising from their extended conjugated structures. To address this limitation, we developed a spatial three-dimensional (3D) multiple-twisted strategy to mitigate photoactivity quenching in porphyrin-based PSs. Leveraging this approach, we designed Crown-TTEP, a crown-ether-based porous organic polymer (POP) with imidazole linkages, synthesized via polymerization of twisted tetra-1,4-di(4-aldehyde phenyl)phenyl-porphyrin (TTEP) and crown-shaped crown ether. This unique architecture enables synergistic crown/photothermal/photodynamic therapy (PTT/PDT). The multiple-twisted 3D structure of Crown-TTEP effectively suppresses aggregation-induced quenching, significantly enhancing photosensitizing activity. In vitro and in vivo studies confirmed broad-spectrum antimicrobial efficacy of Crown-TTEP, demonstrating outstanding additive antibacterial activity against ​​Gram-positive (G