Delivery of DNA vaccines: an overview on the use of biodegradable polymeric and magnetic nanoparticles

Abstract

Vaccination offers a cost-effective approach to the control of endemic infectious and a less invasive treatment modality against cancers. Since the discovery that injecting DNA encoding antigens (expressed in vivo) results in the induction of CD8 T cells as well as antibody mediated immunity, researchers have tried to develop methods to consistently enhance this immunity to disease protective levels in humans. Adsorption, coformulation, or encapsulation with particles has been found to both stabilize DNA formulations, through preventing rapid degradation, and provide vaccine adjuvanting effects, largely due to effective uptake of particulate materials by antigen presenting cells. Recently, it has been shown that nanoparticles, as opposed to microparticles, based DNA vaccine carriers are preferentially taken up by dendritic cells resulting in the induction of maximal levels of combined humoral and cellular immunity.

Applications of immunochemistry in human health: advances in vaccinology and antibody design (IUPAC Technical Report)

“…To induce immunity successfully, the DNA has to be taken up, the encoded protein expressed, and then protein-derived fragments presented on the surface of appropriate cells to the responding T and B cells [62]. Three principal mechanisms of antigen presentation are hypothesized: (1) somatic cell transfection (e.g.…”

“…From several studies, it emerged that nanoparticles in the viral size range (around 40 nm), rather than bacterial-sized microparticles ( > 1000 nm), are superior DNA vaccine carriers, capable of inducing high levels of CD8+ T cells as well as antibodies against the pDNA-encoded antigen [62,86]. Binding of pDNA to carboxylated polystyrene particles via a poly-l-lysine (PLL) linker offering cationic charges that mediate electrostatic binding to the negatively charged DNA strongly enhanced the uptake of DNA by bone-marrow-derived DCs in vitro, and the ability of the DNA to induce potent cellular and humoral immune responses to the encoded antigen in vivo [86].…”

“…These include the ability (1) to protect DNA payload from extracellular degradation, (2) to accommodate large size plasmids and other immunostimulatory agents, (3) to offer a phagocytosis-based passive targeting to APCs, and (4) to be conjugated with appropriate functionalities to enhance target delivery and uptake [62]. Polymeric nanostructures are colloidal carriers ranging in size typically from 1 to 100 nm.…”

“…Their individual size is normally < 100 nm in diameter and is designed to be thermodynamically stable and biocompatible so they may circulate for prolonged periods in the blood. The micellar delivery systems including graft, diblock, or multiblock copolymers possess numerous advantages over liposomes, and have attracted attention as promising gene carriers [62,94,95]; indeed, several micelle gene carriers are being studied in preclinical and clinical trials [62,94]. However, further improvement of polyplex functionality is necessary for enhanced therapeutic efficacy with reduced adverse side effects before these agents can be translated into practical pharmaceutical agents [96][97][98].…”

“…Its good mechanical strength and heat resistance renders silica ideal for protecting the magnetic cores, while its surfaces can be easily functionalized via silane chemistry using organosilanes for covalent attachment of ligands, due to the availability of hydroxyl groups. Functional silanes have been used for bioconjugation of proteins, enzymes, antibodies, cell-targeting agents, and DNA (for references, see [62]). …”