An engineered zinc nanozyme with a core-shell-corona structure combines chemodynamic therapy and immunotherapy and remodels the tumor’s immunosuppressive microenvironment in preclinical models of both primary and metastatic breast cancer.
What was known
Nanozyme-mediated chemodynamic therapy is an emerging anticancer strategy, but its clinical application is hindered by inadequate immunogenic cell death, an immunosuppressive microenvironment and strong immune evasion by tumor cells, factors that favor metastasis and relapse even after treatment.
What this work adds
The authors designed a nanozyme (ZS B TH) with a core-shell-corona structure. Its core is a dual zinc-complexation nanozyme loaded with brefeldin A (BFA, a Golgi apparatus disruptor); the shell is a triphenylphosphine-grafted phospholipid that targets mitochondria, and the corona is hyaluronic acid, which targets tumor cells. The work includes in vitro and in vivo studies.
Main results
After accumulating in tumor cells via the enhanced permeability and retention effect and hyaluronic acid-mediated targeting, the nanozyme degrades and releases the ZST nanozyme, zinc ions and BFA. ZST enters the mitochondria and performs chemodynamic therapy to induce immunogenic cell death, inhibiting growth and metastasis. In parallel, zinc activates the Caspase-1/GSDMD-dependent pyroptosis pathway, enhancing that process, and its overload reduces NAD+ expression and inhibits glycolysis, reversing macrophage polarization from M2 to M1. BFA disrupts the Golgi apparatus to inhibit PD-L1 production and PD-L1-mediated immune evasion. The preclinical results showed high efficacy in suppressing tumor growth and metastasis.
What it means
The work describes a nanomedicine strategy that acts jointly on the tumor and its immune environment. This is preclinical research, in cell and animal models, so its findings are still far from patient use and require safety and efficacy studies in later phases.
Reference: Zhang H, Wang H, Wang H, Liu T, Mu W, Shi X, et al. A dual zinc-complexation nanozyme performs synergistic chemodynamic-immunotherapy along with additional immunosuppressive microenvironment remodeling and immune evasion inhibition for efficient breast cancer treatment. Biomaterials, 2026. DOI.
