[Show abstract][Hide abstract] ABSTRACT: The intracellular delivery of small interfering RNA (siRNA) plays a key role in RNA interference (RNAi) and provides an emerging technique to treat various diseases, including infectious diseases. Chitosan has frequently been used in gene delivery applications, including siRNA delivery. However, studies regarding the modification of chitosan with antibodies specifically targeting T cells are lacking. We hypothesized that chitosan nanoparticles modified with T cell-specific antibodies would be useful for delivering siRNA to T cells. CD7-specific single-chain antibody (scFvCD7) was chemically conjugated to chitosan by carbodiimide chemistry, and nanoparticles were prepared by a complex coacervation method in the presence of siRNA. The mean diameter and zeta potential of the scFvCD7-chitosan/siRNA nanoparticles were approximately 320 nm and +17 mV, respectively, and were not significantly influenced by the coupling of antibody to chitosan. The cellular association of antibody-conjugated nanoparticles to CD4+ T cell lines as well as gene silencing efficiency in the cells was significantly improved compared to nonmodified chitosan nanoparticles. This approach to introducing T cell-specific antibody to chitosan nanoparticles may find useful applications for the treatment of various infectious diseases.
Preview · Article · May 2012 · Bioconjugate Chemistry
[Show abstract][Hide abstract] ABSTRACT: Small interfering RNA (siRNA) has been widely investigated as a potential therapeutic for treatment of various diseases. However, the use of siRNA is limited due to its rapid degradation and low intracellular association in vitro and in vivo. Chitosan nanoparticles encapsulating siRNA were prepared using a coacervation method in the presence of polyguluronate (PG), which is isolated from alginate and is strongly related to ionic interactions of negatively charged alginate. Various physicochemical properties of chitosan/PG nanoparticles, including size, surface charge, morphology, and interaction with siRNA, were characterized. The mean diameter of siRNA-loaded chitosan-based nanoparticles ranged from 110 to 430 nm, depending on the weight ratio between chitosan and siRNA. Nanoparticles showed low cytotoxicity and were useful in delivering siRNA to HEK 293FT and HeLa cells. Chitosan/PG nanoparticles were considered promising for siRNA delivery due to their low cytotoxicity and ability to transport siRNA into cells, which can effectively inhibit induction of targeting mRNA.
No preview · Article · Jul 2009 · Journal of Controlled Release