Work

Tumor redox heterogeneity-responsive nanoparticles for enhanced antitumor efficacy through combining chemo/chemodynamic therapy

Year: 2025

Type: article

Abstract: Cancer represents a significant global health threat, and traditional chemotherapy (CT) often encounters limitations in efficacy due to systemic toxic side effects and tumor heterogeneity. The combination of chemodynamic Therapy (CDT) and CT offers a potential solution to overcome the constraints of single-agent therapies. However, many CT/CDT collaborative systems have critical shortcomings, including insufficient active targeting capabilities, depletion of H 2 O 2 substrates leading to a reduction in CDT effectiveness, and the heterogeneity of redox within tumor cells, which can result ultimately limit overall efficacy. This study developed a redox heterogeneity-responsive CT/CDT nanoparticle, named HFMD, with the goal of overcoming the limitations associated with traditional CT/CDT nanoparticles. In vitro experiments demonstrated that HFMD exhibits redox-sensitive drug release characteristics and the capacity to generate hydroxyl free radicals. Additionally, HFMD enhances H 2 O 2 supply, improves CDT efficiency, and shows significant inhibitory effects on multiple cancer cell lines. In vivo experiments further validated that HFMD possesses excellent tumor-targeting enrichment capabilities and remarkable anti-cancer efficacy, achieving a tumor inhibition rate of approximately 80.1 %. The biological safety assessment indicated that HFMD demonstrates good biocompatibility and successfully mitigates the dose-limiting toxicity associated with free doxorubicin. Overall, this study presents a promising strategy for enhancing anti-cancer efficacy. • The nanoparticle designed to harness the CT/CDT synergy promotes ferroptosis and apoptosis for cancer therapy. • Combines redox heterogeneity responsiveness with ROS bursts within a single nanoparticle. • The excellent therapeutic effect and biosafety of HFMD have potential clinical transformation potential.

Source: International Journal of Pharmaceutics X

DOI: 10.1016/j.ijpx.2025.100455

Authors: Su Cui, Li Yu, Hao Liu, Wenhan Liu, Daiwang Shi

Institutions: First Hospital of China Medical University, China Medical University, Sheng Jing Hospital

Language: English

Topic: Nanoplatforms for cancer theranostics

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,590