State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P. R. China.
CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P. R. China.
Biomacromolecules. 2024 Mar 11;25(3):1602-1611. doi: 10.1021/acs.biomac.3c01141. Epub 2024 Feb 7.
can cause various gastric conditions including stomach cancer in an acidic environment. Although early infections can be treated by antibiotics, prolonged antibiotic administrations may lead to the development of antimicrobial resistance, compromising the effectiveness of the treatments. Antimicrobial peptides (AMPs) have been reported to possess unique advantages against antimicrobial-resistant bacteria due to their rapid physical membrane disruptions and anti-inflammation/immunoregulation properties. Herein, we have developed an AMP hydrogel, which can be orally administered for the treatment of infection. The hydrogel has potent antimicrobial activity against , achieving bacterial eradication within minutes of action. Compared with the AMP solution, the hydrogel formulation significantly reduced the cytotoxicity and enhanced proteolytic stability. experiments suggested that the hydrogel formed at pH 4 had superior therapeutic effects to those at pH 7 and 10 hydrogels, attributed to its rapid release and bactericidal action within the acidic stomach environment. Compared to conventional antibiotic treatments, the AMP hydrogel had the advantages of fast bacterial killing in the gastric juice and obviated proton pump inhibitors during the treatment. Although both the AMP hydrogel and antibiotics suppressed the expression of pro-inflammatory cytokines, the former uniquely promoted inflammation resolution. These results indicate that the AMP hydrogels with effectiveness and biosafety may be potential candidates for the clinical treatment of infections.
可导致各种胃部疾病，包括酸性环境中的胃癌。虽然早期感染可以用抗生素治疗，但长期使用抗生素可能会导致抗菌药物耐药性的发展，从而降低治疗效果。抗菌肽 (AMPs) 由于其快速的物理膜破坏和抗炎/免疫调节特性，被报道对具有抗菌耐药性的细菌具有独特的优势。在此，我们开发了一种 AMP 水凝胶，可口服用于治疗 感染。水凝胶对 具有很强的抗菌活性，在作用几分钟内即可消灭细菌。与 AMP 溶液相比，水凝胶制剂显著降低了细胞毒性并增强了蛋白水解稳定性。 实验表明，在 pH 值为 4 时形成的水凝胶在酸性胃环境中具有比 pH 值为 7 和 10 的水凝胶更好的治疗效果，这归因于其在酸性胃液中的快速释放和杀菌作用。与传统抗生素治疗相比，AMP 水凝胶在治疗过程中具有在胃液中快速杀菌和避免质子泵抑制剂的优点。尽管 AMP 水凝胶和抗生素都抑制了促炎细胞因子的表达，但前者独特地促进了炎症的消退。这些结果表明，具有有效性和生物安全性的 AMP 水凝胶可能是临床治疗 感染的潜在候选药物。
