Larnaudie, Sophie (2017) Supramolecular cyclic peptide-polymer nanotubes as drug delivery vectors. PhD thesis, University of Warwick.

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Abstract

The objective of this thesis is to develop a range of polymeric nanotubes based on self-assembling cyclic peptides suitable to be used as drug delivery systems, and to investigate their behaviour in vitro and in vivo.

The interest for cylindrical structures in a drug delivery context arises from their reported longer circulation times, and enhanced tumour accumulation in vivo compared to spherical nanoparticles. Moreover, supramolecular systems have attracted a lot of attention thanks to their versatility and potential ability to facilitate clearance.

The design of polymeric nanotubes constructed around a cyclic peptide scaffold is described, and various systems are developed. Firstly, the two main synthetic routes (grafting-to and grafting-from) yielding peptide-polymer conjugates are compared in a systematic study, which shows that the two approaches present distinct advantages, and are complementary in nature. This information is then used to design cyclic peptide conjugates specifically directed to drug delivery, using a polymer that combines biocompatible properties and functional handles. Analysis of their self-assembly in solution confirms the cylindrical shape of the obtained supramolecular structures, and a study of their behaviour in vitro and in vivo establishes their potential as delivery systems. Subsequently, the complexation of a highly potent organometallic anticancer agent is described. In vitro studies determined that the use of the nanotubes leads to higher potency and enhanced selectivity towards cancer cells. Finally, a core-shell system designed for drug encapsulation and subsequent pH-triggered release is presented. This approach relies on the use of an amphiphilic and pH responsive system, which in addition confers more stability to the obtained nanotubes.

The work presented in this thesis provides a bottom-up approach in the design of novel self-assembled cyclic peptide nanotubes highly tuned for drug delivery applications.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QD Chemistry
Library of Congress Subject Headings (LCSH):	Drug delivery systems, Supramolecular chemistry, Nanotubes, Cyclic peptides, Self-assembly (Chemistry)
Official Date:	July 2017
Dates:	Date Event July 2017 Submitted
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Perrier, Sébastien
Format of File:	pdf
Extent:	xxvii, 147 leaves : illustrations, charts
Language:	eng

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