No abstract

Engineered nanomaterials promise to transform medicine at the bio–nano interface. However, it is important to elucidate how synthetic nanomaterials interact with critical biological systems before such products can be safely utilized in humans. Past evidence suggests that polyethylene glycol-functionalized (PEGylated) nanomaterials are largely biocompatible and elicit less dramatic immune responses than their pristine counterparts. We here report results that contradict these findings. We find that PEGylated graphene oxide nanosheets (nGO-PEGs) stimulate potent cytokine responses in peritoneal macrophages, despite not being internalized. Atomistic molecular dynamics simulations support a mechanism by which nGO-PEGs preferentially adsorb onto and/or partially insert into cell membranes, thereby amplifying interactions with stimulatory surface receptors. Further experiments demonstrate that nGO-PEG indeed provokes cytokine secretion by enhancing integrin β8-related signalling pathways. The present results inform that surface passivation does not always prevent immunological reactions to 2D nanomaterials but also suggest applications for PEGylated nanomaterials wherein immune stimulation is desired.

Precisely delivering siRNA to its target site in cancer cells is a highdemanding but challenging task. Herein, a biomimetic magnetosome is developed using magnetic nanocluster (MNC) as the core and Arg-Gly-Asp (RGD) decorated macrophage membrane as the cloak, which is achieved via a combination of MNC synthesis, azide-membrane engineering, electrical assembly, and click chemistry. Such a feature-packed magnetosome enables us to gain the success of high-performance siRNA delivery through superior stealth effect, magnetic resonance imaging, magnetic accumulation, RGD targeting, and favorable cytoplasm trafficking. As a result, target gene expression can be significantly suppressed and tumor growth is effectively inhibited, while the systemic toxicity is not notable. These results together vote the biomimetic magnetosome as a promising siRNA delivery system for anticancer therapy.