EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer
Dhiraj Bhavsar1, Krishnakumar Subramanian2, Swaminathan Sethuraman1
1a Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology , SASTRA University , Thanjavur , India and.
Background:
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.
Objective:
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.
Methods:
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.
Results:
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.
Conclusion:
Our results exhibit that the nanocarrier-mediated silencing of EpCAM gene is a promising strategy to treat epithelial cancers.
Insights
Non-cationic liposomes effectively delivered short interfering RNA (si-RNA) to target cancer cells, significantly reducing tumor volume. This nanocarrier approach offers a promising, non-toxic strategy for epithelial cancer treatment via gene silencing.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Therapeutics
Background:
- RNA interference (RNAi) using short interfering RNA (si-RNA) shows potential for cancer treatment by silencing specific genes.
- Cationic non-viral vectors for gene delivery can cause toxic effects in normal cells, necessitating safer, site-specific delivery methods.
Purpose of the Study:
- To design and develop a non-toxic nanocarrier for site-specific delivery of si-RNA into cancer cells to achieve gene silencing.
Main Methods:
- Non-cationic liposomes encapsulating si-RNA targeting epithelial cell adhesion molecule (EpCAM) were developed.
- Characterization included encapsulation efficiency, colloidal stability, and in vitro/in vivo gene silencing efficacy.
- PEGylated liposomes were conjugated with EpCAM antibodies for targeted delivery.
Main Results:
- PEGylated liposomes achieved 47% si-RNA encapsulation efficiency and demonstrated good colloidal stability.
- Targeted liposomes enhanced cell internalization and significantly downregulated EpCAM gene expression in MCF-7 cells.
- In vivo studies showed a 35% reduction in tumor volume in mice treated with immunoliposomes at a low dose.
Conclusions:
- Nanocarrier-mediated silencing of the EpCAM gene using targeted liposomes is a viable and promising strategy for treating epithelial cancers.
- This approach offers a non-toxic alternative for gene silencing therapies in oncology.
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