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PEGylated Graphene Oxide-Mediated Protein Delivery for Cell Function Regulation

Shen, He, Liu, Min, He, Huixin, Zhang, Liming, Huang, Jie, Chong, Yu, Dai, Jianwu, Zhang, Zhijun
ACS Applied Materials & Interfaces 2012 v.4 no.11 pp. 6317-6323
bioactive properties, biocompatibility, cAMP-dependent protein kinase, cell communication, cell death, cell growth, cytoplasm, enzymatic hydrolysis, graphene, graphene oxide, neoplasms, polyethylene glycol, proteins, ribonucleases, therapeutics
Delivery of proteins into cells may alter cellular functions as various proteins are involved in cellular signaling by activating or deactivating the corresponding pathways and, therefore, can be used in cancer therapy. In this study, we have demonstrated for the first time that PEGylated graphene oxide (GO) can be exploited as a nanovector for efficient delivery of proteins into cells. In this approach, GO was functionalized with amine-terminated 6-armed polyethylene glycol (PEG) molecules, thereby providing GO with proper physiological stability and biocompatibility. Proteins were then loaded onto PEG-grafted GO (GO-PEG) with high payload via noncovalent interactions. GO-PEG could deliver proteins to cytoplasm efficiently, protecting them from enzymatic hydrolysis. The protein delivered by GO-PEG reserves its biological activity that regulates the cell fate. As a result, delivery of ribonuclease A (RNase A) led to cell death and transport of protein kinase A (PKA) induced cell growth. Taken together, this work demonstrated the feasibility of PEGlyated GO as a promising protein delivery vector with high biocompatibility, high payload capacity and, more importantly, capabilities of protecting proteins from enzymatic hydrolysis and retaining their biological functions.