Glutathione Depletion-Induced ROS/NO Generation for Cascade Breast Cancer Therapy and Enhanced Anti-Tumor Immune Response

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2024 Mar 12

PMID 38469056

Authors

Jing Wang

Yanxiang Sang

Weijian Chen

Liang Cheng

Wenxiang Du

Hongjie Zhang

Benyan Zheng

Lei Song

Yuan Hu

Xiaopeng Ma

Affiliations

Soon will be listed here.

Abstract

Introduction: As an effective alternative choice to traditional mono-therapy, multifunctional nanoplatforms hold great promise for cancer therapy. Based on the strategies of Fenton-like reactions and reactive oxygen species (ROS)-mediated therapy, black phosphorus (BP) nanoplatform BP@CuO@L-Arg (BCL) co-assembly of cuprous oxide (CuO) and L-Arginine (L-Arg) nanoparticles was developed and evaluated for synergistic cascade breast cancer therapy.

Methods: CuO particles were generated in situ on the surface of the BP nanosheets, followed by L-Arg incorporation through electrostatic interactions. In vitro ROS/nitric oxide (NO) generation and glutathione (GSH) depletion were evaluated. In vitro and in vivo anti-cancer activity were also assessed. Finally, immune response of BCL under ultrasound was investigated.

Results: CuO was incorporated into BP to exhaust the overexpressed intracellular GSH in cancer cells via the Fenton reaction, thereby decreasing ROS consumption. Apart from being used as biocompatible carriers, BP nanoparticles served as sonosensitizers to produce excessive ROS under ultrasound irradiation. The enhanced ROS accumulation accelerated the oxidation of L-Arg, which further promoted NO generation for gas therapy. In vitro experiments revealed the outstanding therapeutic killing effects of BCL under ultrasound via mechanisms involving GSH deletion and excessive ROS and NO generation. In vivo studies have illustrated that the nanocomplex modified the immune response by promoting macrophage and CD8+ cell infiltration and inhibiting MDSC infiltration.

Discussion: BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation, making a new multitherapy strategy for cascade breast cancer therapy.

Citing Articles

Nanotherapeutics for Macrophage Network Modulation in Tumor Microenvironments: Targets and Tools.

Li R, Huang J, Wei Y, Wang Y, Lu C, Liu J Int J Nanomedicine. 2024; 19:13615-13651.

PMID: 39717515 PMC: 11665441. DOI: 10.2147/IJN.S491573.

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