Membrane-anchoring naphthalimide-based aggregation-induced emission photosensitizers for NIR fluorescence imaging and photodynamic elimination of multidrug-resistant bacteria
Acta Biomaterialia, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.actbio.2026.06.014
- Dergi Adı: Acta Biomaterialia
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Compendex, EMBASE, INSPEC, MEDLINE
- Anahtar Kelimeler: Aggregation-induced emission, Antibacterial photodynamic therapy, Membrane targeting, Multidrug-resistant bacteria, Wound healing
- Erciyes Üniversitesi Adresli: Evet
Özet
Multidrug-resistant (MDR) bacterial infections demand antibacterial strategies that circumvent conventional resistance pathways and enable localized action with minimal host toxicity. Photodynamic therapy (PDT) represents a non-invasive approach; however, its effectiveness is constrained by insufficient bacterial targeting, aggregation-caused quenching, and limited reactive oxygen species (ROS) generation under physiological conditions. Herein, we develop two membrane-anchoring naphthalimide-based aggregation-induced emission (AIE) photosensitizers, TPAPV-NIM-mPy-M and TPAPV-NIM-Py-M, engineered via a donor–π–acceptor molecular design to integrate near-infrared (NIR) fluorescence imaging and antibacterial PDT. Both photosensitizers display visible-light absorption, pronounced AIE characteristics, and NIR emission, providing bright signals upon aggregation and facilitating rapid bacterial visualization. Under low-intensity white-light irradiation, they efficiently generate ROS via both type I and type II pathways, supporting oxygen-dependent and partially oxygen-tolerant mechanisms. The introduction of cationic pyridinium units promotes rapid bacterial binding and membrane-specific localization in Gram-positive and Gram-negative bacteria, thereby confining ROS at the bacterial envelope and enhancing photoinactivation. Notably, TPAPV-NIM-Py-M, benefiting from extended π-conjugation and stronger intramolecular charge transfer, exhibits higher ROS output and superior antibacterial efficacy against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), vancomycin-resistant Enterococcus faecium (VR E. faecium), and multidrug-resistant Escherichia coli (MDR E. coli), while maintaining negligible dark toxicity. Cytotoxicity and hemolysis assays confirm a favorable biocompatibility profile. TPAPV-NIM-Py-M also shows strong antibiofilm activity. Furthermore, TPAPV-NIM-Py-M enables effective in vivo photodynamic elimination of bacteria in an E. coli -infected wound model, significantly accelerating wound closure and tissue regeneration without systemic toxicity. This work establishes a membrane-targeted molecular engineering strategy for high-performance AIE photosensitizers and highlights their potential for image-guided photodynamic treatment of MDR bacterial infections and infected wounds. Statement of Significance Antibiotic resistance and biofilm-associated infections are driving demand for non-antibiotic antibacterial therapies. This study introduces naphthalimide-based aggregation-induced emission photosensitizers that anchor to bacterial membranes, enabling near-infrared fluorescence imaging and localized generation of reactive oxygen species for photodynamic killing. Membrane targeting improves efficacy against both Gram-positive and Gram-negative pathogens, including multidrug-resistant strains, and supports treatment of infected wounds in vivo with good biocompatibility. The work provides a general molecular design strategy for image-guided antimicrobial photodynamic therapy.