Cationic porphyrin-based covalent organic frameworks for enhanced phototherapy and targeted chemotherapy of bacterial infections

Abstract

Bacterial infections significantly impede wound healing and threaten global public health. Porphyrin covalent organic frameworks (COFs) have shown promise as phototherapy antibacterial materials. However, the inherent π–π stacking interactions between the monomers also lead to aggregation and quenching of photosensitizers, thereby reducing the production of singlet oxygen (¹O₂) and compromising their antibacterial efficacy. Herein, we designed and prepared a novel cationic porphyrin-based COFs nanoplatform (TAPP-VIO), utilizing photosensitive TAPP and cationic VIO as structural units. This multifunctional nanoplatform is specifically tailored for targeted phototherapy and chemotherapy against bacterial infections. Upon irradiation, TAPP unit in TAPP-VIO generates heat and ¹O₂, which effectively disrupt bacterial structure and cause cell death. The incorporation of VIO unit introduces electrostatic repulsion between layers, mitigating π-π stacking effects and enhancing ¹O₂ production. Additionally, the positive charge imparted by the VIO unit enables TAPP-VIO to bind efficiently to negatively charged bacterial surfaces, immobilizing the bacteria and reducing their motility, thereby improving the overall efficacy of phototherapy. Under identical experimental conditions and concentrations, TAPP-VIO exhibits a ¹O₂ generation capacity that is 179% higher than that of nonionic porphyrin COF. Moreover, the temperature increase induced by TAPP-VIO is 85% of that observed with nonionic porphyrin COF (TAPP-MMA-Da), which is conducive to enhancing the phototherapeutic effects while minimizing heat-induced damage to healthy tissues. In summary, our study presents a straightforward approach to developing non-antibiotic antibacterial nanoagents, and the as-prepared TAPP-VIO is a promising candidate drug suitable for clinical trials in the future.