Coordination-Driven Programming of MOF Stability via Targeting Protein Corona Engineering for Hypoxia-Relieving Sonodynamic Therapy.

Authors

Youjung Sim, Gyeongseok Yang, Joohan Nam, Seungo Baek, Jung Heum Yoon, Jinhyu Lee, Hong Kyu Lee, Jaewoo Lee, Eunshil Choi, Gun Kim, Wonyoung Choe, Ja-Hyoung Ryu

Published in

Biomacromolecules. Volume 27. Issue 9. Pages 6033-6043. Sep 14, 2026.

Abstract

Zr-based metal-organic frameworks (MOFs) are promising nanomedicine platforms, but their rapid degradation in phosphate-rich biological environments remains a critical barrier to clinical translation. Here, incorporating MnOx into the porphyrinic Zr-MOF PCN-224 modulates the coordination environment of Zr6 clusters, suppressing phosphate-induced linker displacement and extending structural integrity under physiological conditions. The optimized 1:1 MnOx@PCN-224 formulation resists phosphate-triggered disassembly and porphyrin release in phosphate-buffered saline (PBS). MnOx also acts as a catalase mimic, converting endogenous H2O2 into O2 to relieve tumor hypoxia and potentiate sonodynamic therapy (SDT). Under high-intensity focused ultrasound (HIFU) irradiation, stabilized porphyrin linkers generate enhanced 1O2 levels. Functionalization with GST-EGFR as a preadsorbed targeting protein corona enables tumor-specific delivery, and the resulting nanoplatform suppresses tumor growth in a 4T1 breast tumor model. This coordination-driven strategy transforms the inherent lability of Zr-MOFs into a designable parameter for engineering biointerface stability for in vivo therapeutic applications.

PMID:
42734277
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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