Organoid-Based Assessment of Metal–Organic Framework (MOF) Nanomedicines for Ex Vivo Cancer Therapy

作者：Dan Li, Rui Zhang, Yinpeng Le, Ting Zhang, Dandan Luo, Han Zhang, ­Jun Li­, Ruibo Zhao, Yeting Hu, Xiangdong Kong · 发表于：ACS Applied Materials & Interfaces · 年份：2024 · DOI：10.1021/acsami.4c05172 · 被引用次数：22 · 研究领域：Nanoparticle-Based Drug Delivery、Nanoplatforms for cancer theranostics、Metal-Organic Frameworks: Synthesis and Applications

Nanomaterials have been extensively exploited in tumor treatment, leading to numerous innovative strategies for cancer therapy. While nanomedicines present immense potential, their application in cancer therapy is characterized by significant complexity and unpredictability, especially regarding biocompatibility and anticancer efficiency. These considerations underscore the essential need for the development of ex vivo research models, which provide invaluable insights and understanding into the biosafety and efficacy of nanomedicines in oncology. Fortunately, the emergence of organoid technology offers a novel approach to the preclinical evaluation of the anticancer efficacy of nanomedicines in vitro . Hence, in this study, we constructed intestine and hepatocyte organoid models (Intestine-orgs and Hep-orgs) for assessing intestinal and hepatic toxicity at the microtissue level. We utilized three typical metal–organic frameworks (MOFs), ZIF-8, ZIF-67, and MIL-125, as nanomedicines to further detect their interactions with organoids. Subsequently, the MIL-125 with biocompatibility loaded methotrexate (MTX), forming the nanomedicine (MIL-125-PEG-MTX), indicated a high loading efficiency (82%) and a well-release capability in an acid microenvironment. More importantly, the anticancer effect of the nanomedicine was investigated using an in vitro patient-derived organoids (PDOs) model, achieving inhibition rates of 48% and 78% for PDO-1 and PDO-2, respectively, demonstrating that...