Spontaneous Protein Adsorption on Graphene Oxide Nanosheets Allowing Efficient Intracellular Vaccine Protein Delivery

Abstract

Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation. Here, we demonstrate that GOx nanosheets can spontaneously adsorb proteins by a combination of interactions. This property is then explored for intracellular protein vaccine delivery, in view of the potential of GOx nanosheets to destabilize lipid membranes such as those of intracellular vesicles. Using a series of in vitro experiments, we show that GOx nanosheet adsorbed proteins are efficiently internalized by dendritic cells (DCs: the most potent class of antigen presenting cells of the immune system) and promote antigen cross-presentation to CD8 T cells. The latter is a hallmark in the induction of potent cellular antigen-specific immune responses against intracellular pathogens and cancer.

Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

“…Carbon-based nanoparticles, such as carbon nanotubes and graphene, have also been studied as vaccine carriers [122,123]. Owing to their high aspect ratio and large surface area, these carbon-based nanoparticles may carry a high proportion of antigens for immune activation.…”

Graphene and the Immune System: A Romance of Many Dimensions

“…GBMs might also prove advantageous as antigen carriers. Li et al (101) exploited the fact that GO can spontaneously adsorb proteins to explore the use of this material for intracellular vaccine delivery. Using an in vitro model, the authors could show that GO adsorbed proteins were efficiently internalized by DCs leading to antigen cross-presentation to CD8+ T cells.…”

Synthetic virus-like particles prepared via protein corona formation enable effective vaccination in an avian model of coronavirus infection

“…In protein-rich media, strong nanoparticle/protein association occurs spontaneously as a means to passivate surface energies, and the resulting particles are encased in a protein layer that dictates the particles' interactions with the environment [10,11]. While protein corona formation is gaining increasing scientific interest owing to its implications in biomedical applications [10,12,13], we herein demonstrate harnessing this phenomenon can be beneficial towards mimicking viral features for vaccine applications. We show that synthetic virus-like particles (sVLPs) with close semblance to native virions in physicochemical properties and antigen display can be facilely prepared through spontaneous antigen-particle association in optimized incubation conditions.…”