Dipeptide nanotubes for biomedical applications

Ultrashort dipeptides based on the FF motif can self-assemble into discrete peptide nanotubes, which have been investigated over the last decade for their potential in the biomedical field. Understanding and controlling the variables which govern the self-assembly process is key to producing an ideal nanoparticle and unlocking the potential of peptide nanotubes. While there has been a lot of investigation into this area, there is a lack of direct comparisons between nanoparticle characteristics and their biomedical efficacy. To this end, a small library of FF and FF analogues were synthesised (NH<sub style="color: rgb(32, 31, 30); font-family: Calibri, Helvetica, sans-serif;">2</sub>-FF-COOH, NH<sub style="color: rgb(32, 31, 30); font-family: Calibri, Helvetica, sans-serif;">2</sub>-ff-COOH and NH<sub style="color: rgb(32, 31, 30); font-family: Calibri, Helvetica, sans-serif;">2</sub>-FF-NH<sub style="color: rgb(32, 31, 30); font-family: Calibri, Helvetica, sans-serif;">2</sub>) and characterised, detailed in Chapter 2. Chapter 3 focuses on the biocompatibility of the peptide nanotubes against a variety of mammalian cells, and Chapter 4 investigates the ability of the peptide nanotubes to act as drug carriers. The final experimental chapter elucidates the antimicrobial efficacy of the nanotubes. The key findings of this work highlight that mammalian cells tolerate relatively high concentrations of the peptide nanotubes, which were also able to efficiently load sodium fluorescein, a small hydrophilic tracer molecule. The drug release profiles revealed that for future applications the burst release from the nanotubes would need to be modified to achieve a satisfactory sustained release profile. The final highlight was the significant activity of the NH<sub style="color: rgb(32, 31, 30); font-family: Calibri, Helvetica, sans-serif;">2</sub>-FF-COOH and NH<sub style="color: rgb(32, 31, 30); font-family: Calibri, Helvetica, sans-serif;">2</sub>-ff-COOH analogues against Gram-positive bacteria, which also extended to biofilm forms of the bacteria, which had not previously been investigated at the time of publishing. In summary, this work demonstrates the great potential of peptide nanotubes in biomedical applications, with future work possibly involving the repurposing and delivery of existing drugs.<br/><i><br/>Thesis embargoed until 31 December 2026</i>.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2021

Author dc:creator

• Porter, Simon

Advisors dc:contributor.advisor

• Laverty, Garry
• McCarthy, Helen

• Peptide nanotubes
• nanoparticle
• drug delivery
• antimicrobials

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/734e8253-e81c-44e2-87ae-a8c8c3d05d6c

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/734e8253-e81c-44e2-87ae-a8c8c3d05d6c