NIR-triggered synergistic Photothermal therapy and type I photodynamic therapy using supramolecular porphyrin-Phthalocyanine assemblies for the treatment of multidrug-resistant bacterial infections.

Multidrug-resistant bacterial infections, such as methicillin-resistant Staphylococcus aureus (MRSA), pose a severe global health threat exacerbated by the limitations of conventional antibiotics and the hypoxic microenvironment of infections. To address this, we developed a novel supramolecular photosensitizer, TAPc@TMAP, via electrostatic self-assembly of anionic 2,3,9,10,16,17,23,24-octacarboxyphthalocyanine (TAPc) and cationic 5,10,15,20-tetrakis(4-trimethylammoniophenyl) porphyrin tetraiodide (TMAP). This nanocomposite exhibits exceptional near-infrared (NIR) responsiveness at 808 nm, enabling synergistic type-I photodynamic therapy (PDT) and photothermal therapy (PTT). Under NIR irradiation, TAPc@TMAP generated superoxide radicals (O2•-) with 55% efficiency retention under hypoxic conditions, significantly outperforming individual components (TAPc and TMAP), and achieved a photothermal conversion efficiency of 31.9% with negligible degradation over five cycles. In vitro, TAPc@TMAP eradicated 99.69% of MRSA at 30 μM concentration under 808 nm laser radiation (0.5 W/cm2, 30 min), inducing bacterial membrane rupture as confirmed by scanning electron microscopy. In a murine model of MRSA-infected wounds, TAPc@TMAP-mediated phototherapy reduced the residual wound area to 14.19 ± 1.9% within 12 days (vs. 33.11 ± 14% in controls) and decreased bacterial burden by 95.96% at day 8. Histological and immunohistochemical analyses revealed attenuated inflammation (22.65% reduction in TNF-α expression, p < 0.001), enhanced angiogenesis (5.06% increase in CD31-positive microvessels, p < 0.001), and organized collagen deposition. This study demonstrates the robust antibacterial efficacy and wound healing promotion of TAPc@TMAP via oxygen-independent type-I PDT/PTT synergy, offering a promising strategy for combating multidrug-resistant bacterial infections.