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In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2017 Jul 05; Vol. 25 (7), pp. 1588-1595. Date of Electronic Publication: 2017 Apr 28. - Publication Year :
- 2017
-
Abstract
- Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs.<br /> (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemistry
Cholesterol chemistry
Cholesterol metabolism
Colorectal Neoplasms genetics
Colorectal Neoplasms mortality
Colorectal Neoplasms pathology
Dihydroxyphenylalanine chemistry
Dihydroxyphenylalanine metabolism
Disease Models, Animal
Drug Carriers
Drug Synergism
Female
HCT116 Cells
Humans
Liver Neoplasms genetics
Liver Neoplasms mortality
Liver Neoplasms secondary
Mice
Mice, Nude
MicroRNAs administration & dosage
MicroRNAs metabolism
Nanostructures chemistry
Organoplatinum Compounds chemistry
Oxaliplatin
Polyethylene Glycols chemistry
Polyethylene Glycols metabolism
Survival Analysis
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Colorectal Neoplasms therapy
Gene Expression Regulation, Neoplastic
Liver Neoplasms therapy
MicroRNAs genetics
Nanostructures administration & dosage
Organoplatinum Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 25
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 28457664
- Full Text :
- https://doi.org/10.1016/j.ymthe.2017.04.005