Issue 15, 2025, Issue in Progress

Manganese-based nanoparticles plus gambogic acid targeted hypoxic tumor microenvironment by enhancing ROS generation and provided antitumor treatment and improved immunotherapy

Abstract

Colorectal cancer (CRC) remains a major global health challenge, particularly in advanced stages where drug resistance leads to high recurrence rates and poor survival outcomes. This study investigates a novel therapeutic approach combining gambogic acid (GA) with manganese dioxide (MnO2) nanoparticles (MBG NPs) to enhance anti-tumor efficacy in the acidic and hypoxic tumor microenvironment (TME). The development of MBG NPs involved conjugating MnO2 nanosheets with bovine serum albumin (BSA) for effective GA encapsulation, optimizing the delivery of both components. We explored the potential of Mn2+ ions released from MnO2 to synergize with GA to alleviate tumor hypoxia and modulate the TME, thereby improving immune response. In vitro assays demonstrated significant cytotoxicity of MBG NPs against mouse colon cancer cells (CT26 cells), with enhanced apoptosis and elevated reactive oxygen species (ROS) levels. In vivo studies using BALB/c mice showed that treatment with MBG NPs significantly reduced tumor volumes and improved survival rates compared to controls. Additionally, MBG NPs combined with programmed death-1 inhibitor (aPD-1) further augmented therapeutic effects. Histological analyses confirmed tumor necrosis and changes in TME composition, indicating the potential of this synergistic strategy to overcome drug resistance in microsatellite stable (MSS) CRC, inhibit tumor growth and benefit patient survival. These findings highlight the promising application of nanoparticle-based platforms in enhancing immunotherapy outcomes for advanced colorectal cancer.

Graphical abstract: Manganese-based nanoparticles plus gambogic acid targeted hypoxic tumor microenvironment by enhancing ROS generation and provided antitumor treatment and improved immunotherapy

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Article information

Article type
Paper
Submitted
04 Dec 2024
Accepted
17 Mar 2025
First published
11 Apr 2025
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2025,15, 11283-11292

Manganese-based nanoparticles plus gambogic acid targeted hypoxic tumor microenvironment by enhancing ROS generation and provided antitumor treatment and improved immunotherapy

Z. Liang, X. Xu, N. Wang, X. He, X. Han, L. Sang, J. Hu and X. Qian, RSC Adv., 2025, 15, 11283 DOI: 10.1039/D4RA08547G

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