超声降解联合上转换发光纳米粒子-姜黄素共轭复合物光动力治疗MRSA型假体周围感染的实验研究

Studies have shown that the failure rate of treatments for periprosthetic joint infection (PJI) with methicillin-resistant Staphylococcus aureus (MRSA) after total joint arthroplasty is very high. Biofilms play a key role in reducing PJI treatment efficacy. Curcumin, the active component of tumeric, has been shown to exhibit antibacterial activity and photosensitivity. Extensive preclinical studies have used it as a photosensitizer in the photodynamic therapy of a wide range of human diseases. Our previous studies proved promising outcomes of curcumin used in photodynamic therapy to eradicate in vitro clinical isolated of planktonic MRSA and MRSA biofilm. Based on these findings, we plan first to synthesize upconversion nanoparticles conjugated with curcumin to improve the hydrosolubility and stability of curcumin and to extend topical delivery of curcumin in vivo. We use the upconversion nanoparticles to act as a transducer to convert near infrared light into excitating light of curcumin, which takes effect by phototoxicity through production of singlet oxygen radicals to kill bacteria. Conjugated compounds are also used to resolve the therapeutic limitation of curcumin in photodynamic therapy for deep tissue infection. Second, we will evaluate in vitro the effect of upconversion nanoparticles conjugated with curcumin under near infrared light on MRSA eradication. The biological effects of conjugated compounds on fibroblast and osteoblast cells will also be explored. The third step is to establish a MRSA-infected knee PJI model in rabbits. Finally using the model, the efficacies of conjugated compounds under near infrared light combined with sonication in eradicating PJI MRSA biofilm will be studied in vivo. Our study will provide new ideas for the treatment of PJI and lay a theoretical foundation for photodynamic therapy in PJI.

研究证实耐甲氧西林金黄色葡萄球菌（MRSA）所致假体周围感染（PJI）治疗失败率很高，生物膜在其中起着关键作用；姜黄素具有抗菌功能及光敏性，已应用于光动力治疗疾病的各领域。前期研究发现姜黄素可在激光照射下对MRSA产生有效杀伤。据此我们拟构建上转换发光纳米粒子-姜黄素共轭复合物，通过纳米载体增加姜黄素的水溶性和稳定性，并延长其于体内循环时间及提高靶向部位的药物浓度；通过上转换发光纳米粒子将近红外光转换以激发体内姜黄素产生光化学效应，突破光动力治疗深部组织感染受辐照光波长限制的局限；首先体外实验验证共轭复合物在近红外线辐照下对MRSA的杀伤作用，并研究其对成纤维及成骨细胞的生物学影响；进而构建PJI动物模型，并联合对PJI治疗有辅助作用的超声波降解，体内研究共轭复合物在近红外线照射下对PJI MRSA生物膜的杀伤抑制效应。为PJI的的治疗提供新的诊疗视角，并为光动力治疗PJI奠定理论基础。

研究证实耐甲氧西林金黄色葡萄菌（MRSA）所致的人工关节置换术后假体周围感染（PJI）的治疗失败率很高，生物膜在其中起着关键作用；姜黄素具有抗菌功能及光敏性，已应用于光动力治疗疾病的各研究领域。前期研究发现姜黄素可在激光照射下对MRSA产生有效杀伤。据此我们构建了上转换发光纳米粒子-姜黄素共轭复合物，通过纳米载体增加姜黄素的水溶性和稳定性，并延长其于体内循环时间及提高靶向部位的药物浓度；通过上转换发光纳米粒子将近红外光转换以激发体内姜黄素产生光化学效应，突破光动力治疗深部组织感染受辐照光波长限制的局限；首先体外实验验证共轭复合物在近红外线辐照下对MRSA的杀伤作用，并研究了其对成纤维及成骨细胞的生物学影响；进而构建PJI动物模型，并联合对PJI治疗有辅助作用的超声波降解，体内研究共轭复合物在近红外线照射下对PJI MRSA生物膜的杀伤抑制效应。为PJI的的治疗提供了新的诊疗视角，并为光动力治疗PJI奠定了理论基础。