Evaluating novel therapeutic approaches for treating rheumatoid arthritis

Within this thesis, we outline two independent projects that highlight two important aspects in targeted therapeutics in RA with one focussing on diagnostics and the other drug delivery. Despite their distinctive aims, both concepts indicate towards potentially more efficient and better means of treating diseased patients. Diagnostics and therapeutics in rheumatoid arthritis are highly advanced however, the degree of personalisation to the patient and specificity remains a problem in this field. Previous research suggests that radiolabelling the chimeric CD20 monoclonal antibody Rituximab, can identify diseased joints by PET/CT scan but is unable to differentiate between the myeloid and lymphoid pathotype. It was therefore hypothesised that using a different CD20 antibody (clone 2H7; Biolegend) would be more efficient at distinguishing B cell rich inflamed synovial tissue from other subtypes. Ultimately, CD20 shows great promise to allow diagnosis of those patients with a higher likelihood of responding well to Rituximab. Techniques used in this thesis suggest that this novel biomarker may provide a possible new means of identifying lymphoid pathotype patients by a non-invasive and more cost-effective method, such as PET/CT scan. Nanocarriers have been investigated profusely, especially in the field of cancer, for use in therapeutics. Nanobubbles armed with a targeting peptide 3.1, NB-3.1, were evaluated for their ability to localise specifically to the inflamed synovium in hopes of allowing delivery of therapeutic drugs with additional efficiency and precision to diseased joints in the future. Peptide 3.1 has been shown to bind only diseased synovial joints and be capable of targeting various therapies to the affected sites. What remains to be investigated are the characteristics and functional capabilities of this peptide-3.1 armed nanobubble combination and a means of standardising between batches, which have shown degrees of variability. By using different imaging techniques and functional assays, NB-3.1 was seen to be capable of localising to their respective targets and carry out their hypothesised function. Additionally, NB-3.1 showed promising results in terms of bypassing immune response and low levels of toxicity, allowing an optimistic outlook for the future. Overall, NB-3.1 may prove to be an extremely beneficial delivery method after further assessments and optimisation of the production process has been carried out.