Nanomechanical Analysis of Living Small Extracellular Vesicles to Identify Gastric Cancer Cell Malignancy Based on a Biomimetic Peritoneum

Sep 21, 2026

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Gastric cancer is among the most prevalent digestive malignancies, and limited in vitro peritoneal models restrict mechanistic studies of peritoneal metastasis. This work constructs a biomimetic peritoneum that replicates microstructure, composition, and key functions, enabling in vitro recurrence of the metastasis process. Using the model, the relationship between sEV mechanical properties and gastric cancer invasiveness is identified. Nanomechanical analysis shows sEV Young’s modulus distinguishes malignant ascites from nonmalignant peritoneal lavage, and ascites-derived sEVs induce mesothelial-to-mesenchymal transition to promote peritoneal metastasis.

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ABSTRACT

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1. INTRODUCTION

This article is licensed under CC-BY-NC-ND 4.0 [www.acsnano.org](www.acsnano.org) Nanomechanical Analysis of Living Small Extracellular Vesicles to Identify Gastric Cancer Cell Malignancy Based on a Biomimetic Peritoneum Zhixing Ge,∇ Songchen Dai,∇ Haibo Yu, * Junhua Zhao, Wenguang Yang, Wenjun Tan, Jingxu Sun, Quan Gan, Lianqing Liu, * and Zhenning Wang* Cite This: ACS Nano 2024, 18, 6130−6146 Read Online | ACCESS | Metrics & More | | Article Recommendations | | *sı Supporting Information | | --- | --- | --- | --- | --- | --- | ABSTRACT: Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective in vitro peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer’s peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process in vitro. Based on this model, the association between the mechanical properties ofsEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young’s modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients’ ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments. KEYWORDS: sEVs, biomimetic peritoneum, peritoneal metastasis, gastric cancer, mesothelial-to-mesenchymal transition, nanomechanical analysis 1. INTRODUCTION As one of the most prevalent malignant tumors, the end stage of gastric cancer (GC) is peritoneal metastasis, which is the major cause of death in patients.1 Therefore, there is an urgent need to explore the mechanisms of peritoneal metastasis. Until now, several studies have shown that peritoneal metastasis of GC is associated with changes in the peritoneal microenvironment.2 The British surgeon Stephen Paget revealed that the transfer of malignant tumors is not a random event but rather is determined by interactions between metastatic cancer cells (“seeds”) and the microenvironment of specific organs (“soil”).3 Therefore, it is of great significance to explore microenvironmental changes during the occurrence and development of peritoneal metastasis. An appropriate in vitro peritoneal model is needed to explore the underlying mechanism of peritoneal metastasis in GC, since animal models do not grant the ability to continuously monitor the process of metastasis. Some researchers have preliminarily explored the construction of biomimetic peritoneum models. Kenny et al. mixed fibroblasts with extracellular matrix (ECM) and covered them with a layer of mesothelial cells to form a bionic peritoneum.4,5 Asano et al. accumulated fibroblasts and mesothelial cells to simulate the peritoneum.6 Furthermore, De Jaeghere et al. and Herbert et al. each reported a hybrid hydrogel scaffold, which was suitable | Received: March 11, 2023
Revised: February 3, 2024
Accepted: February 8, 2024
Published: February 13, 2024 | | | --- | --- | © 2024 The Authors. Published by American Chemical Society 6130 [https://doi.org/10.1021/acsnano.3c02285](https://doi.org/10.1021/acsnano.3c02285) ACS Nano 2024, 18, 6130−6146 Article Figure 1. Schematic diagram of bionic construction, mesothelial-to-mesenchymal transition (MMT), and peritoneal metastasis. (a) Composition and bionic constr

FAQs

Why is a biomimetic in vitro peritoneal model needed for gastric cancer research?

Effective mechanistic exploration of gastric cancer peritoneal metastasis is hindered by the lack of effective in vitro peritoneal models. An appropriate model is required to study the process continuously without relying on animal monitoring.

How does the biomimetic peritoneum in this study support metastasis research?

The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, enabling recurrence of the peritoneal metastasis process in vitro.

What role does nanomechanical analysis of living sEVs play in identifying gastric cancer malignancy?

Nanomechanical analysis reveals that the Young’s modulus of sEVs can differentiate malignant clinical samples (ascites) from nonmalignant clinical samples (peritoneal lavage).

How do ascites-derived sEVs influence peritoneal metastasis in the study?

Ascites-derived sEVs stimulate mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis of gastric cancer.

Sep 21, 2026

Uploaded by Finn