期刊
BIOMATERIALS
卷 210, 期 -, 页码 94-104出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.04.028
关键词
Nontoxic; Nanovehicle; Nanoscale coordination polymers; miRNA; Metastasis; miR-655-3p
资金
- NIH CBI Training Grant [NIH 5T32GM008720-15]
- National Cancer Institute [1R01CA216436-01A1]
- University of Chicago Medicine Comprehensive Cancer Center [NIH CCSG: P30 CA014599]
- Ludwig Institute for Metastasis Research
Though early detection and treatment of primary tumors has significantly improved in recent years, metastatic disease remains among the most significant challenges in cancer therapy. Cancer cells can disseminate before the primary tumor is detected to form micro or gross metastases, requiring toxic systemic therapies. To prevent and suppress metastases, we have developed a nontoxic, long-circulating nanoscale coordination polymer (NCP) protecting microRNA (miRNA) in circulation and releasing it in tumors. Pt-IV(en)(2) [en = ethylenediamine] containing NCPs (PtEN) can release a nontoxic, kinetically inert Pt-II(en)(2) compound and carbon dioxide which aids the endosomal escape of its miRNA cargo, miR-655-3p. Without the presence of the PtEN core, the miRNA showed cellular uptake but no effect. When transfected into human colorectal HCT116 cells by NCPs, this oligometastatic miRNA limited proliferation and epithelial-to-mesenchymal transition by preventing beta-catenin nuclear translocation and tumor cell invasion. Systemic administrations of PtEN/miR-655-3p sustained effective transfection to reduce liver colonization and tumor burden in a xenogenic hepatic metastatic model of HCT116 without any observable toxicity.
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