Anti-epithelial cell adhesion molecule RNA aptamer-conjugated liposomal doxorubicin as an efficient targeted therapy in mice bearing colon carcinoma tumor model.

Abstract

To overcome the lack of selectivity and nonspecific biodistribution of drugs in the body, targeted delivery of chemotherapeutic agents with aptamers is a very effective method. In this strategy, aptamers could be specifically identified and attach to targeted molecules on the cancerous cells and deliver the chemotherapeutic agents to desired tissue with minimal or no damage to the normal cells. In this study, we designed anti-epithelial cell adhesion molecule (EpCAM) RNA aptamer conjugated PEGylated liposomal doxorubicin (ER-lip) to investigate its in vitro and in vivo anticancer abilities. Data showed that EpCAM aptamer was able to enhance cell uptake and cytotoxic effects of Dox in C26 cell line. The biodistribution study indicated that ER-lip enhanced the tumor accumulation of Dox compared to Caelyx. Also, double staining of isolated tumor cells with anti-CD44-PE-cy5 and anti-EpCAM Cy-7 antibodies indicated that tumor cells expressed a high level of EpCAM+ CD44+ cells (p ≤ .001) compared to cultured C26 cell line. in vivo results showed that ER-lip promoted survival and reduced tumor growth rate in animal model compared to Caelyx. In conclusion, these results suggested that the ER-lip could be served as promising formulation for the treatment of cancers with the high expression of EpCAM.

• Authors: Mohammad Mashreghi, Parvin Zamani, Maryam Karimi, Amin Mehrabian, Mahdieh Arabsalmani, Javad Zarqi, Seyedeh Alia Moosavian, Mahmoud Reza Jaafari
• Journal: Biotechnology progress (Biotechnol Prog) Vol. 37 Issue 3 Pg. e3116 (05 2021) ISSN: 1520-6033 [Electronic] United States
• PMID: 33369269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 American Institute of Chemical Engineers.

Chemical References

• Antineoplastic Agents
• Aptamers, Nucleotide
• Epithelial Cell Adhesion Molecule
• liposomal doxorubicin
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacokinetics, pharmacology)
• Aptamers, Nucleotide (chemistry, metabolism, pharmacokinetics)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Doxorubicin (analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
• Drug Delivery Systems (methods)
• Epithelial Cell Adhesion Molecule (chemistry, metabolism)
• Female
• Mice
• Mice, Inbred BALB C
• Polyethylene Glycols (chemistry, pharmacokinetics, pharmacology)
• Tissue Distribution