Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi Do, 14662, South Korea.
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112, USA.
Biomaterials. 2021 Apr;271:120745. doi: 10.1016/j.biomaterials.2021.120745. Epub 2021 Mar 12.
Helicobacter pylori (H. pylori) infection is closely associated with the development of gastric inflammatory diseases and cancer. However, the continued abuse and misuse of antibiotics has accelerated the spread of antibiotic-resistant strains, which poses a tremendous challenge for antibiotic-based H. pylori treatment. In this study, a H. pylori-targeting photodynamic therapy (PDT) system is proposed that multiple 3'-sialyllactose (3SL)-conjugated, poly--lysine-based photosensitizer (p3SLP). p3SLP facilitates H. pylori-targeting PDT via the specific interaction between 3SL and sialic acid-binding adhesin (SabA) in the H. pylori membrane. p3SLP can be orally administered to H. pylori infected mice and irradiated using an endoscopic laser system. The gastrointestinal pathological analysis of the H. pylori-infected mice demonstrated significant H. pylori specific antibacterial effects of PDT without side effects to normal tissue. In addition, an anti-inflammatory response was observed at the site of infection after p3SLP treatment. Consequently, this study demonstrates the superior efficacy of anti-H. pylori PDT with p3SLP in H. pylori-infected mice, and this approach shows great potential for replacing antibiotic-based therapy.
幽门螺杆菌(H. pylori)感染与胃炎症性疾病和癌症的发展密切相关。然而,抗生素的滥用和误用加速了抗生素耐药菌株的传播,这对基于抗生素的 H. pylori 治疗构成了巨大挑战。在本研究中,提出了一种针对 H. pylori 的光动力疗法(PDT)系统,该系统由多个 3'-唾液酸乳糖(3SL)缀合的聚赖氨酸基光敏剂(p3SLP)组成。p3SLP 通过 3SL 与 H. pylori 膜中的唾液酸结合黏附素(SabA)之间的特异性相互作用,促进 H. pylori 靶向 PDT。p3SLP 可以口服给予 H. pylori 感染的小鼠,并使用内镜激光系统进行照射。对 H. pylori 感染小鼠的胃肠道病理分析表明,PDT 具有针对 H. pylori 的显著抗菌作用,而对正常组织没有副作用。此外,在 p3SLP 治疗后,在感染部位观察到抗炎反应。因此,本研究证明了 p3SLP 在 H. pylori 感染小鼠中抗 H. pylori PDT 的优越疗效,这种方法显示出替代基于抗生素的治疗的巨大潜力。