Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo

Abstract

Carbon nanotubes (CNTs) have shown marked capabilities in enhancing antigen delivery to antigen presenting cells. However, proper understanding of how altering the physical properties of CNTs may influence antigen uptake by antigen presenting cells, such as dendritic cells (DCs), has not been established yet. We hypothesized that altering the physical properties of multi-walled CNTs (MWNTs)-antigen conjugates, e.g. length and surface charge, can affect the internalization of MWNT-antigen by DCs, hence the induced immune response potency. For this purpose, pristine MWNTs (p-MWNTs) were exposed to various chemical reactions to modify their physical properties then conjugated to ovalbumin (OVA), a model antigen. The yielded MWNTs-OVA conjugates were long MWNT-OVA (~ 386 nm), bearing net positive charge (5.8 mV), or short MWNTs-OVA (~ 122 nm) of increasing negative charges (− 23.4, − 35.8 or − 39 mV). Compared to the short MWNTs-OVA bearing high negative charges, short MWNT-OVA with the lowest negative charge demonstrated better cellular uptake and OVA-specific immune response both in vitro and in vivo. However, long positively-charged MWNT-OVA showed limited cellular uptake and OVA specific immune response in contrast to short MWNT-OVA displaying the least negative charge. We suggest that reduction in charge negativity of MWNT-antigen conjugate enhances cellular uptake and thus the elicited immune response intensity. Nevertheless, length of MWNT-antigen conjugate might also affect the cellular uptake and immune response potency; highlighting the importance of physical properties as a consideration in designing a MWNT-based vaccine delivery system.

Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy

“…OVA−treated BM−DCs showed no signs of maturation. Incubation of BM−DCs with S −/+ alone has been shown previously to not affect the expression of these molecules [7]. Taken together the data suggest that maturation of BM−DCs induced by (OVA)S −/+ (CpG) or S −/+ (OVA−CpG) was CpG−dependant.…”

“…We have previously demonstrated that altering the surface chemistry of multi−walled CNTs (MWNTs) conjugated to the model antigen ovalbumin (OVA) can affect the extent of their cellular internalization into APCs, and thus the intensity of the resulting immune responses elicited in vitro and in vivo [7]. As a delivery vector for tumour antigens, MWNTs have markedly improved antitumour immune response against breast or liver cancer–derived tumour proteins in vitro [8] or in vivo [9], respectively.…”

Interactions Between Nanoparticles and Dendritic Cells: From the Perspective of Cancer Immunotherapy

“…(3) NPs protect some antigens, such as peptides, from degradation by proteases ( 17 , 18 ). (4) Using NPs as a platform, co-delivery of two or even more moieties can be realized to achieve stronger immune responses ( 17 – 25 ). Widely used combinations include tumor antigens together with adjuvants such as Toll-like receptor agonists ( 18 , 23 – 30 ), or antigens with siRNAs, which silence immunosuppressive genes ( 31 ).…”

Application of carbon nanotubes in cancer vaccines: Achievements, challenges and chances

“…In 2014 Faria et al have reported the delivery of antigen and adjuvant to APCs using CNTs [107]. In this study the model antigen OVA and the TLR9 agonist CpG were both In a previous study, we compared the efficacy of MWNTs functionalised using 1,3−dipolar cycloaddition, oxidation or amide coupling reactions in delivering non−covalently immobilised OVA to APCs [118]. The MWNTs functionalised via amide coupling were more efficient in enhancing the OVA−specific immune response both in vitro and in vivo.…”

“…The first step in the rational design of a CNT based delivery vehicle should be the systematic evaluation of physical traits and surface modifications in order to improve cytosolic delivery. Our group has looked into some of the modifications of CNTs and has shown that relatively minor changes in structure can cause vast differences in immunogenicity though we have not been able to attribute this to improved cytosolic delivery [118]. Future work should continue and expand upon this.…”