多分支金Nanodendrite@ZIF-67负载替拉帕扎明用于肿瘤微环境-对癌症类器官的活化破坏
Multi-Branched Au Nanodendrite@ZIF-67 Loaded with Tirapazamine for Tumor Microenvironment-Activated Disruption of Cancer Organoids.
摘要(中文译文)
肿瘤微环境响应型纳米药物在提高治疗特异性、降低全身毒性方面具有显著优势。然而，单模式治疗的治疗效果常受肿瘤异质性限制，因此需要开发能够利用多种肿瘤微环境特征实现高效协同治疗的多模式纳米平台。本研究开发了一种多功能纳米复合材料，该材料由包裹金纳米枝晶的钴基沸石咪唑酯骨架-67共载替拉扎明构成，用于肿瘤选择性治疗。为解决传统临床前模型的固有局限性，研究采用人健康结直肠癌类器官作为先进的评估平台。机制研究表明，多分支金纳米枝晶可破坏细胞膜完整性，而酸性条件诱导钴基沸石咪唑酯骨架-67降解，促进药物的靶向释放。这些协同作用共同放大细胞内活性氧的产生并破坏线粒体膜，从而导致肿瘤细胞的选择性清除。本研究提出了一种高效的肿瘤微环境响应型纳米治疗平台，并证明了基于类器官的评估系统在推进靶向纳米药物临床转化中的重要价值。
Abstract
Tumor microenvironment-responsive nanomedicines offer significant advantages in enhancing treatment specificity and minimizing systemic toxicity. Nevertheless, the therapeutic efficacy of single-modality treatments is often limited by tumor heterogeneity, necessitating the development of multimodal nanoplatforms capable of leveraging multiple tumor microenvironment characteristics for efficient synergistic therapy. In this study, a multifunctional nanocomposite comprising cobalt zeolitic imidazolate framework-67-encapsulated Au nanodendrites coloaded with tirapazamine is developed for tumor-selective therapy. To address the inherent limitations of traditional preclinical models, human healthy and colorectal cancer organoids are utilized as advanced assessment platforms. Mechanistic studies revealed that multibranched Au nanodendrites disrupt cellular membrane integrity, whereas the acidic condition induces the degradation of the cobalt zeolitic imidazolate framework-67, facilitating targeted drug release. These combined actions synergistically amplify intracellular reactive oxygen species generation and disrupt mitochondrial membranes, leading to the selective elimination of tumor cells. This work presents a highly efficient, tumor microenvironment-responsive nanotherapeutic platform and demonstrates the critical value of organoid-based evaluation systems in advancing the clinical translation of targeted nanomedicines.
如何引用
AMA
Hangyang Ling, Rui Zhang, Jiaxin Niu, Gongxian Sun, Xu Sun, Yao Li, et al. Multi-Branched Au Nanodendrite@ZIF-67 Loaded with Tirapazamine for Tumor Microenvironment-Activated Disruption of Cancer Organoids.. ACS applied materials & interfaces. 2026; doi:10.1021/acsami.6c05735.
APA
Hangyang Ling, Rui Zhang, Jiaxin Niu, Gongxian Sun, Xu Sun, Yao Li, et al (2026). Multi-Branched Au Nanodendrite@ZIF-67 Loaded with Tirapazamine for Tumor Microenvironment-Activated Disruption of Cancer Organoids.. ACS applied materials & interfaces. https://doi.org/10.1021/acsami.6c05735
GB/T 7714
Hangyang Ling, Rui Zhang, Jiaxin Niu, Gongxian Sun, Xu Sun, Yao Li, et al. Multi-Branched Au Nanodendrite@ZIF-67 Loaded with Tirapazamine for Tumor Microenvironment-Activated Disruption of Cancer Organoids.[J]. ACS applied materials & interfaces, 2026 doi:10.1021/acsami.6c05735.
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