Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in Vivo

Abstract

This paper demonstrates how the shape and size of gold nanoparticles (AuNPs) affect immunological responses in vivo and in vitro for the production of antibodies for West Nile virus (WNV). We prepared spherical (20 and 40 nm in diameter), rod (40 × 10 nm), and cubic (40 × 40 × 40 nm) AuNPs as adjuvants and coated them with WNV envelope (E) protein. We measured anti-WNVE antibodies after inoculation of these WNVE-coated AuNPs (AuNP-Es) into mice. The 40 nm spherical AuNP-Es (Sphere40-Es) induced the highest level of WNVE-specific antibodies, while rod AuNP-Es (Rod-Es) induced only 50% of that of Sphere40-E. To examine the mechanisms of the shape-dependent WNVE antibody production, we next measured the efficiency of cellular uptake of AuNP-Es into RAW264.7 macrophage cells and bone-marrow-derived dendritic cells (BMDCs) and the subsequent cytokine secretion from BMDCs. The uptake of Rod-Es into the cells proceeded more efficiently than those of Sphere-Es or cubic WNVE-coated AuNPs (Cube-Es), suggesting that antibody production was not dependent on the uptake efficiency of the different AuNP-Es. Cytokine production from BMDCs treated with the AuNP-Es revealed that only Rod-E-treated cells produced significant levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18), indicating that Rod-Es activated inflammasome-dependent cytokine secretion. Meanwhile, Sphere40-Es and Cube-Es both significantly induced inflammatory cytokine production, including tumor necrosis factor-α (TNF-α), IL-6, IL-12, and granulocyte macrophage colony-stimulating factor (GM-CSF). These results suggested that AuNPs are effective vaccine adjuvants and enhance the immune response via different cytokine pathways depending on their sizes and shapes.

Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro

“…TNF-α and IL-1β have been investigated, since they are involved in lung diseases by the activation of different (pro-)inflammation pathways and the inflammasome activation pathway. 43 We did not measure significant amounts of pro-inflammatory and inflammasome cytokines in most of the AuNP treated cells. Only PEG-COOH AuNPs induced a significant TNF-α release at all tested concentrations, whereas the highest concentration of PVA-NH2 and (PEG + PVA)-NH2 AuNPs induced release of IL-1β.…”

“…Niikura et al 43 employed AuNPs of different sizes and shapes to immune cells and stated that TNF-α and IL-1β were not significantly secreted when RAW264.7 macrophages were exposed to 20 nm spherical AuNPs, while for other AuNPs with different shape (i.e. nanorods, nanocubes) significant cytokine secretion was observed.…”

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

“…Of these characteristics, the particle size is a crucial factor which determines NP endocytosis pathway [17,18], uptake rate and efficiency [6,16,[19][20][21][22], in vitro cytotoxicity [23][24][25][26][27][28], immune responses [27][28][29][30], and the final localisation [15,31,32]. Thus size-dependent uptake of various NPs has been intensively investigated and widely reported.…”

Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and autophagic mitochondrial fission in NSCLC cells

“…[16][17][18] Furthermore, AuNPs are also exploited as a novel class of antitumor agents in cancer therapy through inhibiting angiogenesis and ablating the tumor microvasculature, 19 enhancing chemosensitivity of cancer cells by reversing epithelial-mesenchymal transition, 20 preventing tumor growth and metastasis via abrogating growth factor signaling cascades, 21 and boosting the antitumor immune response as a vaccine platform. 22 These results strongly demonstrate that AuNPs may serve as self-therapeutic nanoparticles in cancer treatment. 23 As highly dynamic organelles in a living cell, mitochondria undergo complementary fission and fusion, forming networks of varying size and dimensions.…”