Self-amplifying disruption of redox and calcium homeostasis by a cascade nanoreactor for synergistic colorectal cancer therapy.

Authors

Yuli Lv, Dejie Ge, Xuan Luo, Shengqi Wang, Nian Liu, Yirui Zhang, Cheng Zhang

Published in

Journal of colloid and interface science. Volume 729. Pages 141820. Oct 16, 2026. Epub Oct 16, 2026.

Abstract

Colorectal cancer remains a leading cause of cancer-related mortality. MnO₂-based chemodynamic therapy combined with CaO₂-mediated calcium overload is limited by weak therapeutic interconnection and antioxidant and calcium-homeostatic defenses in the tumor microenvironment. Here, we constructed a folate (FA)-functionalized hollow mesoporous MnO₂ nanoreactor via interfacial in situ CaO₂ mineralization and curcumin (CUR) loading (FA-HMn@CaC). Upon entering the TME, MnO₂ depleted GSH and generated hydroxyl radicals via Mn²⁺-mediated Fenton-like reactions, while CaO₂ supplied H₂O₂ for CDT amplification and released Ca²⁺ to trigger calcium overload. CUR further inhibited calcium efflux, sustaining Ca²⁺ accumulation and reinforcing the oxidative stress‑calcium overload cascade. In vitro, FA-HMn@CaC dose-dependently reduced intracellular GSH to approximately 30% of the untreated control and increased the total apoptotic rate to 77.0%, whereas the CUR-free FA-HMn@Ca group showed an apoptotic rate of 55.8%. In vivo, FA-HMn@CaC significantly reduced tumor volume (70.8%) compared to PBS and to the single-agent groups, without exhibiting obvious systemic toxicity. Unlike previous MnO₂/CaO₂ systems that mainly co-deliver CDT and calcium overload, this work addresses calcium efflux-the bottleneck that otherwise terminates intracellular Ca²⁺ elevation-linking calcium overload and GSH-depleted CDT into a mutually reinforcing cascade.

PMID:
42901115
Bibliographic data and abstract were imported from PubMed on 21 Oct 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.