Nanoparticle Delivery of Oligometastasis-associated microRNA Inhibits Growth of Colorectal Metastases
Abstract
Introduction: In patients with liver metastasis from CRC, some present with “oligometastatic” disease that is limited in number of metastases and respond favorably to local therapies. We previously found that several... [ view full abstract ]
Introduction: In patients with liver metastasis from CRC, some present with “oligometastatic” disease that is limited in number of metastases and respond favorably to local therapies. We previously found that several microRNA clustered on 14q32 are upregulated in oligometastasis as compared to polymetastasis. These miRNAs repress cellular pathways of adhesion, invasion and motility. In this study, we use nanoparticles to deliver oligometastasis-associated, 14q32-encoded miRNA miR655 into liver metastases, and show this strategy can effectively inhibit liver metastasis progression in a murine xenogenic model of CRC. Methods: Splenic injection of the luciferase/tdTomato dual-labelled HCT116 cells were performed on athymic nude mice to generate liver metastases. Mice were treated with nanoparticles labelled with Alexa647 and carrying miR655 twice a week for 4 weeks. Tumor burden was quantified by in vivo luminescent and ex vivo fluorescent imaging. qPCR was used to measure gene expressions of TGFBRS and ICK, two known targets of miR655. Results: We treated 3 groups of metastases bearing mice with nanoparticle carrying non-targeting microRNA or miR655. Highly selective co-localization of tdTomato and Alexa647 occurred post-injection. The fluorescence from HCT116 tumors were 4.3-fold lower in the miR655 group at 4wks. The number of tumor colonies in miR-655 group is decreased at 4wks. TGFBR2 and ICK expression is decreased by 63% and 73% respectively, in the miR655 group. Conclusion: Nanoparticle delivery of oligometastasis-associated microRNAs is targeted and effective in the suppression of liver metastasis. Our model of liver metastasis is a robust platform to test potential adjuvant therapies for liver metastatic disease.
Authors
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Lai Xue
(University of Chicago)
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Ralph Weichselbaum
(University of Chicago)
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Mitchell Posner
(University of Chicago)
Topic Areas
Colorectal Surgery , Surgical Oncology
Session
Plenary » Plenary Scientific Session (10:25 - Friday, 22nd September, Bradley Lecture Center)