research
Publication
Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System (COVER)
2023.11.16Jun-Young Park, Sung Jean Park, Jun Young Park, Sang-Hyun Kim, Song Kwon, YunJae Jung*, and Dongwoo Khang*
The plasma proteins around nanoparticles
(NPs) form an outer protein corona, significantly influencing the subsequent
immune response. However, it was uncertain whether the protein corona around
NPs influences immune response. This study clarified that the immune response
mediated by the protein corona is greatly dependent on the type of plasma
proteins surrounding the NPs. Structural changes in the unfolded protein corona
elevated reactive oxygen species (ROS) levels and induced major proinflammatory
cytokine release in both murine and human macrophage cell lines. In contrast,
negligible structural changes in the protein corona provoke neither ROS
production nor proinflammatory cytokine release. Furthermore, in vivo analysis
confirms that a stimulated immune response by an unfolded protein corona
triggers selective activation of innate and adaptive immunity in the spleen.
Specifically, neutrophils, natural killer cells, and CD8+ T cells are
overpopulated by unfolded protein corona structures surrounding nanotubes,
whereas innate and adaptive immunologic responses are not triggered by a normal
protein corona. In conclusion, highly unfolded protein corona structures are
strongly correlated with subsequent activation of proinflammatory cytokines and
innate immune responses; thus, the protein corona can be used in
immune-enhancing therapy