Graphene based nanomaterials are being used experimentally to deliver therapeutic agents to cells or tissues both in vitro and in vivo. However, substantial challenges remain before moving to safe and effective use in humans. In particular, it is recognised that graphene molecules undergo complex interactions with solutes, proteins or cellular systems within the body, and that these interactions impact significantly on the behaviour or toxicity of the molecule. Approaches to overcome these problems include modification of the graphene or its combination with other molecules to accentuate favourable characteristics or modify adverse interactions. This has led to an emerging role for graphene as one part of highly-tailored multifunctional delivery vehicles. This review examines the knowledge that underpins present approaches to exploit graphene in therapeutics delivery, discussing both favourable and unfavourable aspects of graphene behaviour in biological systems and how these may be modified; then considers the present place of the molecule and the challenges for its further development.

SummaryWe have used global protein expression analysis to characterize the pathways of dexamethasone-mediated apoptosis and resistance in myeloma. Analysis of MM.1S cells by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) identified a series of proteins that were up-and downregulated following dexamethasone treatment. Downregulated proteins included proteins involved in cell survival and proliferation, whereas upregulated proteins were involved in post-translational modification, protein folding and trafficking. A comparison with published gene expression studies identified FK binding protein 5 (FKBP5) (also known as FKBP51), a key regulatory component of the Hsp90-steroid-receptor complex to be increased at the mRNA and protein level postdexamethasone exposure. Quantitative real time polymerase chain reaction and 2D-PAGE analysis of the dexamethasone resistant cell line MM.1R demonstrated no increase in FKBP5, consistent with its association with dexamethasone-mediated apoptosis. Western blot analysis of FKBP5 and other members of the Hsp90-receptor complex showed an increase in FKBP5 whilst FKBP4 (also known as FKBP52) and Hsp90 expression remained constant. No changes were observed in MM.1R. In conclusion, we demonstrated that following steroid receptor signalling, the cell carries out a number of adaptive responses prior to cell death. Interfering with these adaptive responses may enhance the myeloma killing effect of dexamethasone.

Understanding haematological malignancies at the protein level is important as the development of targeted treatments must be based on knowledge regarding the molecular pathogenesis of the tumour, inherited genetic variation and the mode of action of drugs. 'Proteomics' describes the analysis of the entire proteome of a cell or tissue and incorporates multiple technologies including Western blotting, two-dimensional gel electrophoresis, mass spectrometry, and ProteinChip-based technology. Although there are a limited number of studies to date in haematology those performed highlight the potential future impact of these technologies in the discovery of novel markers, proteins associated with drug resistance and the identification of tumour biomarkers which may facilitate the development of a rapid diagnostic test easily applicable in the clinical setting. Rapid large-scale analysis of the proteome in normal pathways and disease offers the opportunity of identification of potential diagnostic/prognostic markers and proteins associated with the malignant phenotype. This review discusses the current situation regarding the use of these technologies and the potential opportunities their future use may offer in the field of haematology.