Cardiac-targeting peptide-modified Prussian blue nanozymes loaded with Astragaloside IV for efficient ICI-myocarditis therapy.

Authors

Jing Zhou, Jiali Tang, Zehao Huang, Zixuan Liang, Yunxi Huang, Qi Zeng, Chao Yu, Junjie Liu, Yuanyuan Chen, Sida Wang, Nuo Yang, Yan Deng

Published in

Materials today. Bio. Volume 39. Pages 103482. Epub Jul 22, 2026.

Abstract

Immune checkpoint inhibitor (ICI) therapy can trigger immune-related adverse events across multiple organs, and myocarditis remains among the most lethal cardiac manifestations, culminating in arrhythmias and heart failure. Current management primarily relies on ICI interruption and empirical immunosuppression, but this broad strategy lacks heart-targeted precision and does not specifically address the concurrent immune and oxidative components of myocardial injury. Two major challenges therefore remain: insufficient therapeutic exposure within inflamed myocardium and the need to restrain pathogenic immune activation while protecting stressed cardiomyocytes from oxidative damage. Astragaloside IV (AS-IV) is appealing for pleiotropic cardioprotection and immunoregulation, yet limited bioavailability and insufficient myocardial exposure constrain its in vivo efficacy. Here we develop AS@PB-CTP, a cardiac-homing nanozyme integrating Prussian blue (PB) with SOD/CAT/POD-like catalysis, an AS-IV payload, and a cardiac-targeting peptide (CTP). AS@PB-CTP attenuates oxidative stress-induced injury in H₂O₂-challenged HL-1 cardiomyocytes and modulated macrophage-associated phenotypes toward an M2-like state. In the anti-PD-1/cTnI myocarditis model, AS@PB-CTP preferentially accumulates in injured myocardium, reduces leukocyte infiltration and fibrosis, and improves ventricular function, with increased ejection fraction and fractional shortening. Mechanistically, transcriptomic and protein-level analyses identified PI3K-Akt-mTOR signaling as a treatment-associated pathway, while immune profiling revealed coordinated attenuation of splenic IFN-γ⁺CD8⁺ effector T-cell responses and cardiac macrophage-associated inflammation. Collectively, AS@PB-CTP represents a cardiac-targeted redox-immune nanotherapeutic platform that couples catalytic antioxidant activity with immune modulation for ICI-associated myocarditis.

PMID:
42548957
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.