Zn-Quer Nanozymes Reprogram the Malignant Phenotypic Transformation of Gastric Cancer Cells via Cascade Reactive Oxygen Species Coordination

TL;DR

This paper introduces Zn-Quer nanozymes, a new treatment for gastric cancer that reduces harmful cell changes by balancing reactive oxygen species.

Contribution

The novel Zn-Quer nanozyme is introduced as a therapeutic strategy for gastric cancer through ROS coordination and malignant phenotype reprogramming.

Findings

Zn-Quer nanozymes inhibit gastric cancer cell proliferation and induce apoptosis.

The nanozymes reduce intracellular ROS levels and reprogram malignant traits like EMT and angiogenesis.

In vitro and in vivo experiments confirm the effectiveness of Zn-Quer nanozymes in reversing cancerous transformations.

Abstract

Gastric cancer (GC) remains one of the leading causes
of cancer-related
mortality worldwide, presenting significant therapeutic challenges
due to its late-stage diagnosis and high metastatic potential. Imbalance
in reactive oxygen species (ROS) homeostasis is crucial for the onset,
development, and malignant transformation of GC. To address the demand
for innovative therapeutic approaches, this study introduces a novel
nanocoordination polymer, Zn-Quer nanozymes (NZs), synthesized from
quercetin (Quer) and zinc ions. These nanoparticles utilize quercetin’s
anti-inflammatory and antioxidant properties, improving its bioavailability
and therapeutic effectiveness via a nanoparticle delivery system.
Zn-Quer NZs were synthesized via coordination chemistry and characterized
by using TEM, XRD, and FTIR to confirm their structural integrity
and composition. In vitro studies on GC cell lines and in vivo xenograft
model experiments demonstrate that Zn-Quer NZs effectively inhibit
cell proliferation, induce apoptosis, and reprogram malignant phenotypes
such as epithelial-mesenchymal transition (EMT) and angiogenesis,
as indicated by changes in the expression of related markers. Moreover,
Zn-Quer NZs significantly reduce the overall intracellular ROS levels
in epithelial cells under oxidative stress by modulating multiple
steps of ROS generation. These findings underscore Zn-Quer NZs as
a promising therapeutic strategy for gastric cancer, capable of rebalancing
ROS and effectively reversing malignant phenotypic transformation.

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