A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme Cascade

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...

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Main Authors: Man Zhang, Junhao Kou, Zhenyi Song, Ling Qiu, Chunzhao Yang, Qi Xue
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Nanomaterials
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Online Access:https://www.mdpi.com/2079-4991/15/9/670
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author Man Zhang
Junhao Kou
Zhenyi Song
Ling Qiu
Chunzhao Yang
Qi Xue
author_facet Man Zhang
Junhao Kou
Zhenyi Song
Ling Qiu
Chunzhao Yang
Qi Xue
author_sort Man Zhang
collection DOAJ
description 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 H<sub>2</sub>O<sub>2</sub> 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.
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spelling doaj-art-1e5ad8b5ce9c43eeb4329b51eeece2e62025-08-20T02:24:58ZengMDPI AGNanomaterials2079-49912025-04-0115967010.3390/nano15090670A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme CascadeMan Zhang0Junhao Kou1Zhenyi Song2Ling Qiu3Chunzhao Yang4Qi Xue5Department of General Surgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, ChinaCollege of Pharmacy, Xi’an Medical University, Xi’an 710021, ChinaCollege of Pharmacy, Xi’an Medical University, Xi’an 710021, ChinaDepartment of General Surgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, ChinaDepartment of General Surgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, ChinaDepartment of General Surgery, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, ChinaPostoperative 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 H<sub>2</sub>O<sub>2</sub> 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.https://www.mdpi.com/2079-4991/15/9/670Janus protein nanofilmpostoperative recurrence of colorectal cancerabdominal adhesionamyloid-like protein self-assembly
spellingShingle Man Zhang
Junhao Kou
Zhenyi Song
Ling Qiu
Chunzhao Yang
Qi Xue
A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme Cascade
Nanomaterials
Janus protein nanofilm
postoperative recurrence of colorectal cancer
abdominal adhesion
amyloid-like protein self-assembly
title A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme Cascade
title_full A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme Cascade
title_fullStr A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme Cascade
title_full_unstemmed A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme Cascade
title_short A Janus Amyloid-like Nanofilm Inhibits Colorectal Cancer Postoperative Recurrence and Abdominal Adhesion via Synergistic Enzyme Cascade
title_sort janus amyloid like nanofilm inhibits colorectal cancer postoperative recurrence and abdominal adhesion via synergistic enzyme cascade
topic Janus protein nanofilm
postoperative recurrence of colorectal cancer
abdominal adhesion
amyloid-like protein self-assembly
url https://www.mdpi.com/2079-4991/15/9/670
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