Nanoparticle Delivery Of MiR-122 Inhibits Colorectal Cancer Liver Metastasis
Abstract
Liver metastasis is a leading cause of cancer morbidity and mortality. Thus, there has been strong interest in the development of therapeutics that can effectively prevent liver metastasis. One potential strategy is to utilize molecules that have broad effects on the liver microenvironment, such as miR-122, a liver-specific miRNA that is a key regulator of diverse hepatic functions. Here we report the development of a nanoformulation miR-122 as a therapeutic agent for preventing liver metastasis. We engineered a galactose-targeted lipid calcium phosphate (Gal-LCP) nanoformulation of miR-122. This nanotherapeutic elicited no significant toxicity and delivered miR-122 into hepatocytes with specificity and high efficiency. Across multiple colorectal cancer liver metastasis models, treatment with Gal-LCP miR-122 treatment effectively prevented colorectal cancer liver metastasis and prolonged survival. Mechanistic studies revealed that delivery of miR-122 was associated with downregulation of key genes involved in metastatic and cancer inflammation pathways, including several proinflammatory factors, matrix metalloproteinases, and other extracellular matrix degradation enzymes. Moreover, Gal-LCP miR-122 treatment was associated with an increased CD8+/CD4+ T-cell ratio and decreased immunosuppressive cell infiltration, which makes the liver more conducive to antitumor immune response. Collectively, this work presents a strategy to improve cancer prevention and treatment with nanomedicine-based delivery of miRNA.
Recommended Citation
H. Sendi and M. Yazdimamaghani and M. Hu and N. Sultanpuram and J. Wang and A. S. Moody and E. McCabe and J. Zhang and A. Graboski and L. Li and J. D. Rojas and P. A. Dayton and L. Huang and A. Z. Wang, "Nanoparticle Delivery Of MiR-122 Inhibits Colorectal Cancer Liver Metastasis," Cancer Research, vol. 82, no. 1, pp. 105 - 113, American Association for Cancer Research, Jan 2021.
The definitive version is available at https://doi.org/10.1158/0008-5472.CAN-21-2269
Department(s)
Chemical and Biochemical Engineering
International Standard Serial Number (ISSN)
1538-7445; 0008-5472
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2025 American Association for Cancer Research, All rights reserved.
Publication Date
01 Jan 2021
PubMed ID
34753773
Comments
National Institutes of Health, Grant T32CA196589