Modular design of cyclic peptide - polymer conjugate nanotubes for delivery and tunable release of anti-cancer drug compounds.

Autor: Hill SK; Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK., England RM; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield, UK., Perrier S; Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK; Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: S.Perrier@warwick.ac.uk.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Mar; Vol. 367, pp. 687-696. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1016/j.jconrel.2024.01.023
Abstrakt: High aspect-ratio nanomaterials have recently emerged as promising drug delivery vehicles due to evidence of strong cellular association and prolonged in vivo circulation times. Cyclic peptide - polymer conjugate nanotubes are excellent candidates due to their elongated morphology, their supramolecular composition and high degree of pliability due to the versatility in manipulating amino acid sequence and polymer type. In this work, we explore the use of a nanotube structure on which a potent anti-cancer drug, camptothecin, is attached alongside hydrophilic or amphiphilic RAFT polymers, which shield the cargo. We show that subtle modifications to the cleavable linker type and polymer architecture have a dramatic influence over the rate of drug release in biological conditions. In vitro studies revealed that multiple cancer cell lines in 2D and 3D models responded effectively to the nanotube treatment, and analogous fluorescently labelled materials revealed key mechanistic information regarding the degree of cellular uptake and intracellular fate. Importantly, the ability to instruct specific drug release profiles indicates a potential for these nanomaterials as vectors which can provide sustained drug concentrations for a maximal therapeutic effect.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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