Nanoporous layered graphene hydrogel for controlled drug delivery

Abstract

Graphene-related materials with tuneable pore sizes in the nanoscale range offer the potential to address significant challenges in biomolecule separation, controlled delivery of drugs, selective biosensor, rechargeable batteries, supercapacitors and solar cells. Layered assemblies of graphene-related sheets with physical and chemical cross-linkers between the sheets have been recognized as one possible strategy for making such nanoporous materials. However, current approaches give very limited control over the pore size distribution, particularly with regards control of the mean pore size and the degree of spread around it. This work particularly outlined the design, synthesis and characterization of a nanoporous layered graphene hydrogel produced via peptide-mediated self-assembly of reduced graphene oxide (rGO). The peptides have been designed using molecular dynamics (MD) simulation to self-assemble the rGO sheets with a desired inter-sheet spacing (pore size). The hydrogel material was synthesized and characterized using a range of methods to demonstrate the desired pore size is achieved. In the second body of this work, the rGO binding peptide hydrogel, denoted rGOPH, showed to be a promising candidate for the controlled delivery of an anti-cancer drug. In particular, it was shown that the rGOPH has a high doxorubicin (DOX) loading capacity achieved through physical adsorption within its nanoporous structure. Design of experiments (DoE) and statistical analysis on different preparation parameters revealed that pore size and drug loading capacity are tuneable. In the final part of the work, a desirable pH-dependant drug release properties was shown by rGOPH nominating such hydrogels as promising candidates for cancer therapy. In addition, the hydrogel materials exhibited a high biocompatibility to the healthy cells for their attachments and proliferation. The cytotoxicity of the hydrogel materials demonstrated to be low. The work reported in this thesis has provided new computational and experimental understanding for fabrication of graphene based nano-constructs with tuneable pore size as well as new methodologies and approaches. Although the focus was only on one designed peptide, the design and methodologies developed here are quite potent and, therefore, lay the foundations for fabrication of nanoporous graphene based materials of virtually any pore size to suit the needs of users in broader applications (such as nanomedicines, nanobiotechnology, nanoelectronics, biosensors and biomolecular and nanoparticle separations).