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

被引:5
作者
Li, Dan [1 ,2 ]
Zhang, Rui [1 ,2 ]
Le, Yinpeng [1 ,2 ]
Zhang, Ting [1 ,2 ]
Luo, Dandan [1 ,2 ]
Zhang, Han [1 ,2 ]
Li, Jun [3 ]
Zhao, Ruibo [1 ,2 ]
Hu, Yeting [3 ]
Kong, Xiangdong [1 ,2 ]
机构
[1] Zhejiang Sci Tech Univ, Inst Smart Biomed Mat, Sch Mat Sci & Engn, Hangzhou 310018, Peoples R China
[2] Zhejiang Sci Tech Univ, Zhejiang Mauritius Joint Res Ctr Biomat & Tissue E, Hangzhou 310018, Zhejiang, Peoples R China
[3] Zhejiang Univ, Dept Colorectal Surg & Oncol, Key Lab Canc Prevent & Intervent, Minist Educ,Affiliated Hosp 2,Sch Med, Hangzhou 310000, Peoples R China
基金
中国国家自然科学基金;
关键词
organoids; MOF nanomedicines; biocompatibility; anticancerefficiency; theragnostic model; NANOPARTICLES; HEPATOTOXICITY; REDUCTION; MOUSE;
D O I
10.1021/acsami.4c05172
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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 PDOs could predict clinical response and facilitate prospective therapeutic selection. These achievements presented great potential for organoid-based ex vivo models for nano theragnostic evaluation in biosafety and function.
引用
收藏
页码:33070 / 33080
页数:11
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