Department 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.
Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Guangzhou, Guangdong Province, People's Republic of China.
Int J Nanomedicine. 2024 Jun 21;19:6319-6336. doi: 10.2147/IJN.S458520. eCollection 2024.
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.
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).
The DHTPY-Cu@ZOL exhibited proficient HO 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.
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.
本研究创新了一种基于纳米酶的治疗策略，将聚集诱导发光（AIE）光敏剂与铜纳米酶结合。这种方法旨在解决细菌感染中常见的缺氧情况，并通过确保为活性氧（ROS）生成提供足够的氧气供应来提高光动力疗法（PDT）的效果。
我们的方法涉及二羟基三苯乙烯基吡啶（DHTPY）-Cu@zoledronic 酸（ZOL）纳米酶颗粒的合成。我们首先合成 DHTPY，然后将其与铜纳米酶结合形成 DHTPY-Cu@ZOL 复合材料。使用动态光散射、透射电子显微镜和 X 射线光电子能谱等各种技术对纳米酶的尺寸、形态和化学性质进行了表征。我们进行了一系列体外和体内试验，以评估 DHTPY-Cu@ZOL 纳米酶的光动力、抗菌和伤口愈合特性，包括其产氧能力、ROS 产生和对耐甲氧西林金黄色葡萄球菌（MRSA）的抗菌功效。
DHTPY-Cu@ZOL 表现出高效的 HO 清除和氧气生成能力，这对于增强缺氧感染环境中的 PDT 至关重要。我们的体外分析显示对 MRSA 具有显著的抗菌作用，表明纳米酶有可能破坏细菌细胞膜。此外，在使用糖尿病大鼠模型和 MRSA 感染伤口的体内研究中，DHTPY-Cu@ZOL 显著改善了伤口愈合并减少了细菌的存在，突出了其作为慢性感染的非抗生素治疗方法的功效。
我们的研究表明，DHTPY-Cu@ZOL 是一种很有前途的对抗抗生素耐药微生物病原体和生物膜的方法。这些纳米酶颗粒的生物相容性和稳定性，以及它们提高 PDT 效果的能力，使它们成为临床应用的有前途的候选者。
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