EpCAM Aptamer-Functionalized Cationic Liposome-Based Nanoparticles Loaded with miR-139-5p for Targeted Therapy in Colorectal Cancer
Autor: | Xin Liang, Yuyu Zhao, Jiajun Xu, Feng Gao, Lei Ni, Vanminh Le, Shaoyu Li, Qianyi Gong, Jianwen Liu |
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Rok vydání: | 2019 |
Předmět: |
Male
Tumor suppressor gene Colorectal cancer medicine.medical_treatment Mice Nude Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Targeted therapy Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement In vivo Cations Cell Line Tumor Drug Discovery medicine Animals Humans Cationic liposome Cell Proliferation Mice Inbred BALB C Cancer Epithelial cell adhesion molecule Epithelial Cell Adhesion Molecule HCT116 Cells 021001 nanoscience & nanotechnology medicine.disease In vitro Gene Expression Regulation Neoplastic MicroRNAs chemistry Liposomes Cancer research Heterografts Nanoparticles Molecular Medicine Female Colorectal Neoplasms 0210 nano-technology Aptamers Peptide HeLa Cells |
Zdroj: | Molecular Pharmaceutics. 16:4696-4710 |
ISSN: | 1543-8392 1543-8384 |
Popis: | Colorectal cancer (CRC) is one of the most common cancers worldwide. MicroRNAs (miRNAs) play a vital role in a variety of biology processes. Our previous work identified miR-139-5p as a tumor suppressor gene overexpressed in CRC that assisted in inhibiting progression of cancer. The main challenge of miRNAs as therapeutic agents is their rapid degradation in plasma, poor uptake, and off-target effects. Therefore, the development of miRNA-based therapies is necessary. In this study, we developed a cationic liposome-based nanoparticle loaded with miR-139-5p (miR-139-5p-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MNPs) and surface-decorated with epithelial cell adhesion molecule (EpCAM) aptamer (Apt) (miR-139-5p-EpCAM Apt-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MANPs) for the targeted treatment of CRC. The size of MANPs was 150.3 ± 8.8 nm, which had a round-shaped appearance and functional dispersion capabilities. It also showed negligible hemolysis in the blood. MANPs markedly inhibited the proliferation, migration, and invasion of one or more CRC cell lines in vitro. Furthermore, we demonstrated the uptake and targeting ability of MANPs in vivo and in vitro. MANPs inhibit the growth of HCT8 cells in vitro and have a significant tumor suppressive effect on subcutaneous HCT8 colorectal tumor mice. Our results demonstrated that MANPs were an effective carrier approach to deliver therapeutic miRNAs to CRC. |
Databáze: | OpenAIRE |
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