Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment.
Multi-functional vesicles improve Helicobacter pylori eradication by a comprehensive strategy based on complex pathological microenvironment.
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多功能囊泡基于复杂病理微环境的综合策略提高幽门螺杆菌的根除率。
DOI：
10.1016/j.apsb.2022.05.014
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发表时间：
2022-09
影响因子：
14.5
通讯作者：
Hu, Haiyan
中科院分区：
文献类型：
--
作者：
Chen, Xiaonan;Zou, Yiqing;Zhang, Shuqi;Fang, Pengchao;Li, Shuxuan;Li, Pengyu;Sun, Yingying;Yuan, Gang;Hu, Haiyan
关键词：
幽门螺杆菌（H. pylori）全球感染率超50%，因其在体内复杂的病理微环境，给临床治疗带来巨大挑战。为提高根除效果，我们在此制备了一种药物囊泡RHL/Cl - Ch - cal，将胆固醇 - 聚乙二醇、骨化三醇和一线抗生素克拉霉素共载入鼠李糖脂构成的外层脂质层中。RHL/Cl - Ch - cal能够快速穿透胃黏液层，抵达幽门螺杆菌感染部位，随后有效破坏幽门螺杆菌生物被膜结构，杀灭游离的幽门螺杆菌，并抑制残留细菌的重新黏附（称为生物被膜根除四部曲）。此外，RHL/Cl - Ch - cal通过补充胆固醇修复宿主上皮细胞膜上的脂筏，从而激活宿主对幽门螺杆菌的免疫反应。最后，RHL/Cl - Ch - cal通过恢复溶酶体酸化并辅助降解，杀灭细胞内的幽门螺杆菌。在实验中，RHL/Cl - Ch - cal在经典的幽门螺杆菌感染小鼠模型中展现出卓越的抗幽门螺杆菌功效。因此，本研究为抗幽门螺杆菌治疗提供了一种“全面攻击”策略，包括生物被膜根除四部曲、免疫激活和杀灭细胞内细菌。
多功能囊泡RHL/Cl - Ch - cal由鼠李糖脂构成，克拉霉素、胆固醇 - 聚乙二醇和骨化三醇载入其疏水区域，通过生物被膜根除四部曲、免疫激活和杀灭细胞内细菌来提高幽门螺杆菌的根除率。
Helicobacter pylori (H. pylori), creating a global infection rate over 50%, presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo. To improve the eradication efficacy, herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG, calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer. RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H. pylori infection sites, and then effectively destroyed the architecture of H. pylori biofilms, killed dispersed H. pylori and inhibited the re-adhesion of residual bacteria (called biofilms eradication tetralogy). Moreover, RHL/Cl-Ch-cal activated the host immune response to H. pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells. Finally, RHL/Cl-Ch-cal killed the intracellular H. pylori through recovering the lysosomal acidification and assisting degradation. In experiments, RHL/Cl-Ch-cal demonstrated prominent anti-H. pylori efficacy in the classical H. pylori-infected mice model. Therefore, the study provides a “comprehensive attack” strategy for anti-H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing. Multi-functional vesicles RHL/Cl-Ch-cal are composed of rhamnolipid, where clarithromycin, cholesterol-PEG and calcitriol are loaded in the hydrophobic region, which improve Helicobacter pylori eradication through biofilms eradication tetralogy, immune activation and intracellular bacteria killing.
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影响因子：
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通讯作者：
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