Lentinan-Modified Carbon Nanotubes as an Antigen Delivery System Modulate Immune Response in Vitro and in Vivo

Abstract

Adjuvants enhance immunogenicity and sustain long-term immune responses. As vital components of vaccines, efficient adjuvants are highly desirable. Recent evidence regarding the potential of carbon nanotubes (CNTs) to act as a support material has suggested that certain properties, such as their unique hollow structure, high specific surface area, and chemical stability, make CNTs desirable for a variety of antigen-delivery applications. Lentinan, a β-1,3-glucohexaose with β-1,6-branches that is extracted from the mushroom Lentinus edodes, is an effective immunostimulatory drug that has been clinically used in Japan and China, and recent studies have proved that specific beta-glucans can bind to various immune receptors. In this research, we covalently attached lentinan to multiwalled carbon nanotubes (MWCNTs) and tested their ability to enhance immune responses as a vaccine delivery system. In vitro study results showed that the nanotube constructs could rapidly enter dendritic cells and carry large amounts of antigen. Moreover, maturation markers were significantly upregulated versus the control. Thus, lentinan-modified multiwalled carbon nanotubes (L-MWCNTs) were regarded as an effective intracellular antigen depot and a catalyzer that could induce phenotypic and functional maturation of dendritic cells. Furthermore, compared with L-MWCNTs (35 μg/mL), a corresponding concentration of carboxylic carbon nanotubes (C-MWCNTs, 31.8 μg/mL) and an equivalent concentration of lentinan (3.2 μg/mL) did not remarkably influence the immune reaction in vitro or in vivo. Hence, we can hypothesize that the capability of L-MWCNTs was a consequence of the increased intracellular quantity of lentinan grafted onto the nanotubes. Overall, our studies demonstrated that L-MWCNTs significantly increased antigen accumulation in the cells and potentiated cellular and humoral immunity. In conclusion, L-MWCNTs constitute a potential vaccine delivery system to enhance immunogenicity for therapeutic purposes.

A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine

“…Such functionalization has reduced their cytotoxicity and altered the function of immune cells, such as PEG and polyethylenimine (PEI), 76 cationic glycopolymers, 77 vinblastine, 78 and Lentinan. 79 Huang et al reported good results using mice-bearing syngeneic murine squamous cell tumors. They intratemporally injected single-walled CNTs (SWCNTs) and irradiated the cancer cells with a low power NIR laser for 10 minutes.…”

Lentinan from shiitake selectively attenuates AIM2 and non-canonical inflammasome activation while inducing pro-inflammatory cytokine production

“…Various β-glucans have been extracted from sources such as cereals, yeast, bacteria, and fungi 5 . Among β-glucans, lentinan is extracted from bodies of shiitake ( Lentinus edodes ) and is a high molecular weight polysaccharide 2, 6 . Lentinan, a well known biological response modifier, has a β-(1 → 3) linked backbone and two β-(1 → 6) side chains every five residues 2 .…”

“…Lentinan, a well known biological response modifier, has a β-(1 → 3) linked backbone and two β-(1 → 6) side chains every five residues 2 . Lentinan enhances the cytotoxic activities of primary macrophages and RAW264.7 cell lines and was found to elevate cytotoxic activity and tumor necrosis factor (TNF) secretion in macrophages both in vitro and in vivo 2, 6 . In addition, lentinan has been shown to increase peritoneal macrophage cytotoxicity against metastatic tumors 3 .…”

Mannose‐Modified Multi‐Walled Carbon Nanotubes as a Delivery Nanovector Optimizing the Antigen Presentation of Dendritic Cells

“…Another classical approach is to directly bind surfactants, nucleic acids, peptides, polymers or oligomers in a non‐covalent manner . Recently, there have also been reports on the use of carbon nanotubes for the delivery of antigens, but most of them just modified simply to increase their water solubility, which makes them less effective in antigen delivery …”

“…[23][24] Recently, there have also been reports on the use of carbon nanotubes for the delivery of antigens, but most of them just modified simply to increase their water solubility, which makes them less effective in antigen delivery. [25][26][27] In this study, we developed multi-walled carbon nanotubes (MWCNTs) modified with mannose (Man-MWCNTs) as a specific target delivery system to DCs. Compared with passive target delivery, decorating with targeting ligands which can actively recognize specific receptors on the target cell is much more efficient.…”