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Carbon nanotubes (CNTs) cause perturbations in immune systems and limit the application of CNTs in biomedicine. Here we demonstrate that a surface chemistry modification on multiwalled CNTs (MWCNTs) reduces their immune perturbations in mice and in macrophages. The modified MWCNTs change their preferred binding pattern from mannose receptor to scavenger receptor. This switch significantly alleviates NFκB activation and reduces immunotoxicity of MWCNTs.