期刊
NANO LETTERS
卷 21, 期 7, 页码 3225-3236出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c00501
关键词
Cancer Stem-like Cells; Magnetic Actuation; Nanoscale Tether Mobility; Tumor Mechanobiology; Ligand Presentation
类别
资金
- National Natural Science Foundation of China [31570979, 81772394, 11672255]
- Research Grants Council of Hong Kong [14205817, 14204618]
- Health and Medical Research Fund, the Food and Health Bureau
- Government of the Hong Kong Special Administrative Region [04152836]
- Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong
- Hong Kong Research Grants Council [R4017-18]
- Key Program of the Natural Science Foundation of Guangdong Province [2018B0303110003]
- Shenzhen Science and Technology Projects [KQTD20170331100838136, JCYJ20170817172023838, JCYJ20170306092215436, JCYJ20170413161649437]
- Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties [SZGSP007]
- Shenzhen Science and Technology Innovation Commission [JCYJ20170413154735522]
- Early Career Scheme from Research Grants Council of the Hong Kong Special Administrative Region, China [252094/17E]
The use of a magnetic nanoplatform was found to efficiently culture cancer cells with stem cell-like features, aiding in understanding tumor development mechanisms and establishing tumor models. Substrates with high ligand mobility suppressed integrin-mediated mechanotransduction, enhancing cancer cell stemness.
Developing strategies for efficient expansion of cancer stem-like cells (CSCs) in vitro will help investigate the mechanism underlying tumorigenesis and cancer recurrence. Herein, we report a dynamic culture substrate tethered with integrin ligand-bearing magnetic nanoparticles via a flexible polymeric linker to enable magnetic manipulation of the nanoscale ligand tether mobility. The cancer cells cultured on the substrate with high ligand tether mobility develop into large semispherical colonies with CSCs features, which can be abrogated by magnetically restricting the ligand tether mobility. Mechanistically, the substrate with high ligand tether mobility suppresses integrin-mediated mechanotransduction and histone-related methylation, thereby enhancing cancer cell stemness. The culture-derived high-stemness cells can generate tumors both locally and at the distant lung and uterus much more efficiently than the low-stemness cells. We believe that this magnetic nanoplatform provides a promising strategy for investigating the dynamic interaction between CSCs and the microenvironment and establishing a cost-effective tumor spheroid model.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据