EpCAM-targeted liposomal si-RNA delivery for treatment of epithelial cancer

Abstract

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.

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

“…Furthermore, on Day 30, lower tumor volume was indicated for ER‐lip compared with Caelyx which was statistically significant. These data were along with the data of cell toxicity, cell uptake and biodistribution that all confirmed the efficacy of ER‐lip in enhanced targeting of C26 colon cancer cell especially when used as tumor model 42 . Survival results showed that therapy with ER‐lip increased survival time compared to Caelyx.…”

“…These data were along with the data of cell toxicity, cell uptake and biodistribution that all confirmed the efficacy of ER-lip in enhanced targeting of C26 colon cancer cell especially when used as tumor model. 42 Survival results showed that therapy with ER-lip increased survival time compared to Caelyx. Therefore, ER-lip efficiently target tumor cells with enhanced permeation and consequent improve in the Dox accumulation at tumor microenvironment, which results in the increased survival of mice.…”

Recent Advancements in the Design of Nanodelivery Systems of siRNA for Cancer Therapy

“…The nontoxic cationic NCs are preferred to transport siRNA to cancer cells . For example, “ smart cationic PEGylated liposomes are designed that are lipid-free loaded with siRNA and anticancer drug DOX that will selectively target the epithelial cell adhesion molecule (EpCAM) gene and inhibits its expression to decrease the malignancy in epithelial cancers.” In a study, “a novel NC was designed by utilizing unimer polyion conjugate and gold nanocarriers (AuNCs) to selectively transport the siRNA to the site of solid carcinoma to reduce the tumor growth.” Through active transport, the siRNA-loaded NCs boost cellular absorption via receptor-mediated endocytosis. Various choosing ligands can be used to change the surface of the NCs.…”