T Cell-Specific siRNA Delivery Using Antibody-Conjugated Chitosan Nanoparticles

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.

Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma

“…On the other hand, electroporation is not a suitable method for in vivo administration of siRNA [18]. Various delivery systems have been discovered to target T cells, including CD3 targeted polyethylenimine (PEI) [19], CD40L targeted liposomes [20], CD7 targeted chitosan [21] or oligo-arginine [22]. However, their efficiency and potential systemic side effects for asthma therapy remain to be tested.…”

Synthesis and characterization of pH-responsive carboxymethyl chitosan-g-polyacrylic acid hydrogels

“…Chitosan is a copolymer of D-glucosamine and N-acetyl glucosamine derived from chitin. It was reported that chitosan and its derivant carboxymethyl chitosan (CMC) are potentially useful pharmaceutical materials owing to their good biocompatibility and low toxicity [10][11][12]. Tu et al [13] reported the swelling kinetics of a series of carboxymethyl chitosan-g-poly (acrylic acid) hydrogels pretreated under acidic or neutral media for applications in colon-specific drug delivery.…”

PEG-g-Chitosan Nanoparticles Functionalized with the Monoclonal Antibody OX26 for Brain Drug Targeting

“…As a consequence, Cs NPs, obtained by different methodologies [24] (covalent cross-linking, precipitation, self-assembly, spraydrying and ionic cross-linking with tripolyphosphate), were employed in targeted therapy for colon or mucosal delivery [25], cancer treatment [26], or in delivering of vaccines, genes and peptides [27]. Moreover, as Cs NPs are unstable in the bloodstream owing to the activation of the reticuloendothelial system, PEGylation of Cs NPs surface is strongly required [28].…”