EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer
| Autor: | Swaminathan Sethuraman, Uma Maheswari Krishnan, Krishnakumar Subramanian, Dhiraj Bhavsar |
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| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
Small interfering RNA Antibodies Neoplasm Pharmaceutical Science 02 engineering and technology Mice SCID Biology Gene delivery 03 medical and health sciences chemistry.chemical_compound Mice RNA interference In vivo Cell Line Tumor Gene silencing Animals Humans Gene Silencing RNA Small Interfering Liposome Gene Transfer Techniques Epithelial cell adhesion molecule General Medicine Genetic Therapy 021001 nanoscience & nanotechnology Epithelial Cell Adhesion Molecule Molecular biology Cell biology 030104 developmental biology chemistry Cancer cell Liposomes MCF-7 Cells RNA Interference 0210 nano-technology |
| Zdroj: | Drug delivery. 23(4) |
| ISSN: | 1521-0464 |
| Popis: | RNA interference (RNAi) technology using short interfering RNA (si-RNA) has shown immense potential in the treatment of cancers through silencing of specific genes. Cationic non-viral vectors employed for gene delivery exhibit toxic effects in normal cells limiting their widespread use, therefore, site-specific delivery using benign carriers could address this issue.Design of a non-toxic carrier that enables site-specific delivery of si-RNA into the cancer cells is of prime importance to realize the promise of gene silencing.In the present study, non-cationic liposomes encapsulating si-RNA against epithelial cell adhesion molecule (EpCAM) were developed and characterized for encapsulation efficiency, colloidal stability, in vitro and in vivo gene silencing efficacy.PEGylated liposomes containing phosphatidyl choline and phosphatidyl ethanolamine exhibited maximum si-RNA encapsulation efficiency of 47%, zeta potential of -21 mV, phase transition temperature of 51 °C and good colloidal stability in phosphate-buffered saline (PBS) containing bovine serum albumin (BSA) and plasma protein (PP) at 37 °C. Conjugation of epithelial cell adhesion molecule (EpCAM) antibody to the liposomes resulted in enhanced cell internalization and superior down-regulation of EpCAM gene in MCF-7 cell lines when compared with free si-RNA and the non-targeted liposomes. In vivo evaluation of immunoliposomes for their efficacy in regressing the tumor volume in Balb/c SCID mice showed about 35% reduction of tumor volume in comparison with the positive control when administered with an extremely low dose of 0.15 mg/kg twice a week for 4 weeks.Our results exhibit that the nanocarrier-mediated silencing of EpCAM gene is a promising strategy to treat epithelial cancers. |
| Databáze: | OpenAIRE |
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