Zhang Man, Kou Junhao, Song Zhenyi, Qiu Ling, Yang Chunzhao, Xue Qi
Department of General Surgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, China.
College of Pharmacy, Xi'an Medical University, Xi'an 710021, China.
Nanomaterials (Basel). 2025 Apr 28;15(9):670. doi: 10.3390/nano15090670.
Postoperative peritoneal adhesion and high recurrence rates are critical challenges in the clinical treatment of colorectal cancer. In this study, based on amyloid-like protein self-assembly technology, a novel Janus protein film was developed. The protein film encapsulates glucose oxidase (GOx) and catalase (CAT), which is named PTL@GC. Through a one-step method involving cysteine-reduced lysozyme-induced amyloid-like self-assembly, the film was co-loaded with GOx and CAT to achieve synergistic anti-adhesion and anti-tumor recurrence effects. The Janus film features a hydrophobic side that stably adheres to the intestinal surface without exogenous chemical modification and a hydrophilic side that prevents adhesion. The loaded GOx selectively induces disulfidptosis in SLC7A11-overexpressing tumor cells, while CAT degrades HO to alleviate hypoxia and inhibit oxidative stress, significantly reducing adhesion-related fibrosis. The experimental results demonstrate that PTL@GC exhibited excellent mechanical properties, high enzyme activity retention (>90%), and controllable degradability (complete metabolism within 50 days). In animal models, PTL@GC reduced postoperative adhesion area by 22.77%, decreased local tumor burden to 28.42% of the control group, and achieved an inhibition rate of 58.49%, without inducing systemic toxicity. This study presents a biologically safe and functionally synergistic approach to addressing dual complications following colorectal cancer surgery, offering potential insights for future research on multifunctional Janus materials.
术后腹膜粘连和高复发率是结直肠癌临床治疗中的关键挑战。在本研究中，基于淀粉样蛋白自组装技术，开发了一种新型的双面蛋白膜。该蛋白膜包裹了葡萄糖氧化酶（GOx）和过氧化氢酶（CAT），命名为PTL@GC。通过半胱氨酸还原的溶菌酶诱导的淀粉样自组装一步法，该膜共负载了GOx和CAT，以实现协同抗粘连和抗肿瘤复发效果。双面膜具有一个疏水侧，可在无需外源化学修饰的情况下稳定粘附于肠表面，以及一个亲水侧，可防止粘连。负载的GOx选择性地诱导SLC7A11过表达的肿瘤细胞发生二硫键还原型铁死亡，而CAT降解H2O2以减轻缺氧并抑制氧化应激，显著减少粘连相关的纤维化。实验结果表明，PTL@GC表现出优异的机械性能、高酶活性保留率（>90%）和可控的降解性（50天内完全代谢）。在动物模型中，PTL@GC使术后粘连面积减少了22.77%，将局部肿瘤负荷降低至对照组的28.42%，并实现了58.49%的抑制率，且未诱导全身毒性。本研究提出了一种生物安全且功能协同的方法来解决结直肠癌手术后的双重并发症，为未来多功能双面材料的研究提供了潜在的见解。
