ABSTRACT
Gene inhibitors, especially small interfering RNA (siRNA), have been widely studied and are considered to have significant importance in therapeutic application for various diseases. However, several limitations related to delivery of those gene inhibitors have delayed advancement in siRNA therapy. Physical and chemical instability and rapid clearance of genes have been major problems in achieving effective and efficient gene delivery. There have been extensive studies to try to overcome these barriers using several different types of delivery systems for both cellular and systemic delivery. The ultimate goal of these studies is to develop an effective gene delivery system, which can improve the stability of nucleic acid with high biocompatibility. This system should have the capability to induce cellular internalization and endosomal escape, followed by a release of nucleic acid into the cytosol. Despite intensive efforts in developing an effective nanocarrier system, efficient delivery of
nucleic acid is still a rate-limiting step for gene therapy. Here, we have developed two types of membrane/core Nanoparticles (NPs) in order to efficiently deliver siRNA and further its use in therapeutic applications. The first LPD (Liposome-Polycation-DNA) formulation showed efficient delivery of siRNA and a potential therapeutic effect for metastatic lung tumor treatment. The second formulation, referred to as LCP (Lipid-Calcium-Phosphate), was developed in order to improve the limited release of cargo of LPD formulation, which was done by replacing the protamine-DNA core with a pHsensitive calcium phosphate (CaP) core.
