DHTPY-Cu@ZOL-Enhanced Photodynamic Therapy: A Strategic Platform for Advanced Treatment of Drug-Resistant Bacterial Wound Infections

Abstract

Biao Hou,1– 3,* Bo Li,4,* Wanjun Deng,3,* Bo Li,1,2 Bibo Ren,5 Chao Hu,3 Guowei Zhang,1,2 Fen Yang,6 Meimei Xiao,3 Songlin Xie,3 Denghui Xie1,2 1Department of Joint Surgery and Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Hand and Foot Microsurgery, The affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5College of Biomass Science and Engineering, Sichuan University, Chengdu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Denghui Xie; Songlin Xie, Email [email protected]; [email protected]: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme’s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes’ potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.Keywords: copper nanozyme, aggregate induced emission, photodynamic antibacterial therapy, antimicrobial resistance, diabetic wound healing

Keywords

• copper nanozyme
• aggregate induced emission
• photodynamic antibacterial therapy
• antimicrobial resistance
• diabetic wound healing