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

IF 5.9 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2026-09-14 Epub Date: 2026-08-28 DOI:10.1021/acs.biomac.6c00899

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

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引用次数: 0

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.

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基于靶向蛋白电晕工程的低氧声动力治疗MOF稳定性协调驱动规划

锆基金属有机框架（mof）是很有前途的纳米医学平台，但它们在富含磷酸盐的生物环境中的快速降解仍然是临床转化的关键障碍。在这里，将MnOx加入卟啉型Zr-MOF PCN-224中可以调节Zr6簇的配位环境，抑制磷酸盐诱导的连接体位移，并在生理条件下延长结构完整性。优化的1:1 MnOx@PCN-224配方抵抗磷酸盐引发的分解和卟啉在磷酸盐缓冲盐水（PBS）中的释放。MnOx还可以作为过氧化氢酶的模拟物，将内源性H2O2转化为O2，以缓解肿瘤缺氧并增强超声动力治疗（SDT）。在高强度聚焦超声（HIFU）照射下，稳定的卟啉连接物产生增强的1O2水平。在4T1乳腺肿瘤模型中，GST-EGFR作为靶向蛋白冠的功能化实现了肿瘤特异性递送，由此产生的纳米平台抑制肿瘤生长。这种协调驱动的策略将zr - mof的固有性转化为可设计的参数，用于体内治疗应用的工程生物界面稳定性。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.