Systemic miRNA delivery by nontoxic nanoscale coordination polymers limits epithelial-to-mesenchymal transition and suppresses liver metastases of colorectal cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31060867.
- Also identified by DOI 10.1016/j.biomaterials.2019.04.028 and PMC identifier 6579118.
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Abstract
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<sup>IV</sup>(en)<sub>2</sub> [en = ethylenediamine] containing NCPs (PtEN) can release a nontoxic, kinetically inert Pt<sup>II</sup>(en)<sub>2</sub> 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 β-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.
Medical subject headings
- Colorectal Neoplasms
- Epithelial-Mesenchymal Transition
- Gene Transfer Techniques
- Liver Neoplasms
- MicroRNAs
- Nanoparticles
- Polymers