In Vivo Immunological Response of PEGylated Graphene Oxide via Intraperitoneal Injection

Polyethylene glycol functionalization has been believed with the capacity of endowing nanomaterials with stealth characteristics, which can diminish the macrophage arrest and adverse immunological response. However, our study previously provided evidences that polyethylene glycol-functionalized graphene oxide (GOP) stimulated strong immunological response to macrophage despite of non-internalization in vitro, raising the safety concern and potential immunostimulation use of GOP. In light of this finding, we herein systematically study the in vivo immunological response upon the exposure of GOP via intraperitoneal injection. Taking the cytokines production, cell types in peritoneal fluid, biochemical index, hematology and histopathology as in vivo indicators, we demonstrate that GOP still remains the stealth-but-activating capacity on macrophage in a time and dose-dependent manner. Specifically, the immune response can be significantly elevated after high dose of single injection, indicating GOP as a new candidate of adjuvant for immunotherapy. For the low dose of multiple injections, the immune response becomes gentle, temporary, and tolerable, which manifests GOP’s biocompatibility in general drug delivery. Above results thus can provide guidance for safe and rational use of GOP for various biomedical applications.