Peptide functionalized graphene oxide derivatives for drug and gene delivery

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Graphene-based nanomaterials have expanded their applications to biomedicine, ranging from biosensors andimaging to scaffolds for tissue engineering to drug and gene delivery in cancer treatment. In particular,graphene oxide derivatives (GODs) are the main focus of the intensive research in the field of drug/genedelivery, due to their oxygen functionalities that make them soluble in aqueous biological media. GODs caninteract with biological molecules through both covalent and non-covalent bonds that opens up moreopportunities in for targeted drug delivery. Specific targeting, efficient drug release and intracellular traffickingare the most important requirements in a drug delivery system. The GOD delivery performance has yet to beoptimized to meet all these requirements. On the other hand, peptides are an important class of biomaterialbuilding blocks, providing unique bio-functions such as targeting, antimicrobial activity, cell penetration, andimmunotherapy. Here, we propose to explore the possibility of peptide functionalized GODs in drug and genedelivery, in terms of their functional versatility and tunability. The team, consisting of University of Waterlooresearchers and their industry partner, Zerocor, will first try to understand the interaction between peptide andGOD, and the competition among different peptides and therapeutic drugs on GOD binding. This part of studywill provide information on how to construct GOD-based drug carriers that functionalize with different typesof peptides. The physicochemical properties of the GOD-peptide/drug complexes will be investigated andcharacterized using a variety of techniques, to reveal cellular uptake mechanisms and cell membraneinteractions. The team will subsequently study the functions of a selected number of drug-peptide-GODcomplexes, in terms of tumor cell targeting, lysosomal escape and triggered drug/cargo release. Optimizedformulations of GOD/peptide/drug complexes will be tested for their stability in physiologically relevantsolutions by means of size distribution, assembly morphology, drug loading and efficacy. Eventually, themultifunctional GOD-based drug delivery system is expected to be obtained for future in vivo tests.