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Nanoparticle Delivery of miR-122 Inhibits Colorectal Cancer Liver Metastasis.
Sendi, Hossein; Yazdimamaghani, Mostafa; Hu, Mengying; Sultanpuram, Nikhila; Wang, Jie; Moody, Amber S; McCabe, Ellie; Zhang, Jiajie; Graboski, Amanda; Li, Liantao; Rojas, Juan D; Dayton, Paul A; Huang, Leaf; Wang, Andrew Z.
Afiliación
  • Sendi H; Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina.
  • Yazdimamaghani M; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
  • Hu M; UNC School of Pharmacy, Chapel Hill, North Carolina.
  • Sultanpuram N; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
  • Wang J; UNC School of Pharmacy, Chapel Hill, North Carolina.
  • Moody AS; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
  • McCabe E; UNC School of Pharmacy, Chapel Hill, North Carolina.
  • Zhang J; Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina.
  • Graboski A; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
  • Li L; Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, North Carolina.
  • Rojas JD; Dalian Municipal Central Hospital, Dalian, China.
  • Dayton PA; UNC School of Pharmacy, Chapel Hill, North Carolina.
  • Huang L; Joint Department of Biomedical Engineering, University of North Carolina and, North Carolina State University, Chapel Hill, North Carolina.
  • Wang AZ; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
Cancer Res ; 82(1): 105-113, 2022 01 01.
Article en En | MEDLINE | ID: mdl-34753773
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. SIGNIFICANCE: Highly specific and efficient delivery of miRNA to hepatocytes using nanomedicine has therapeutic potential for the prevention and treatment of colorectal cancer liver metastasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / MicroARNs / Nanopartículas / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Res Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / MicroARNs / Nanopartículas / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Res Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos