Hydrogel-Encapsulated Liposomes for Delivery of Therapeutic siRNA to Breast Cancer Cells

Abstract

This project focuses on the development of a hydrogel-encapsulated liposome (‘lipogel’) delivery system for the delivery of small interfering RNA (siRNA) to breast cancer cells. siRNA-based therapeutics show promise for the inhibition of metastatic breast cancer through specific oncogene inhibition. However, the in vivo delivery of siRNA for cancer therapy has been severely limited due to the rapid degradation of ‘naked’ or unprotected siRNA in the bloodstream. Current methods for siRNA delivery suffer from inefficient siRNA loading, difficulty in targeting carriers to specific cells, cytotoxicity, and immunogenicity.

In the design and development of the present lipogel delivery system, the composition of the encapsulated hydrogels was optimized for the application of siRNA encapsulation and delivery to breast cancer cells. These lipogels showed significantly increased encapsulation efficiency of siRNA (1.7-fold) and prolong the sustained release of an encapsulated siRNA analog compared to traditional liposomal drug delivery vehicles. As a result, these lipogels have the potential for allowing a greater amount of siRNA to be delivered to target cells without substantial degradation in the bloodstream. Furthermore, based on cellular uptake studies, it has been shown that soft lipogels show enhanced cellular uptake over stiff lipogels. Furthermore, they allow for siRNA delivery directly to the site of activity in the cell cytoplasm unlike stiff lipogels, which are clustered inside endosomes near the cell nuclei. The significant finding from the optimization of the delivery system developed in this project is that the inclusion of hydrogels with optimal softness within liposomes could provide the benefit of efficient targeted delivery of siRNA as shown in breast cancer cell lines. This observation suggests that lipogel material properties could be tailored to develop similar delivery systems for cancers in other organs as well.