Amphiphilic tri- and tetra-block co-polymers combining versatile functionality with facile assembly into cytocompatible nanoparticles

Vasey, Catherine E.; Pearce, Amanda K.; Sodano, Federica; Cavanagh, Robert; Abelha, Thais; Cuzzucoli Crucitti, Valentina; Anane-Adjei, Akosua B.; Ashford, Marianne; Gellert, Paul; Taresco, Vincenzo; Alexander, Cameron

Abstract

In order for synthetic polymers to find widespread practical application as biomaterials, their syntheses must be easy to perform, utilising freely available building blocks, and should generate products which have no adverse effects on cells or tissue. In addition, it is highly desirable that the synthesis platform for the biomaterials can be adapted to generate polymers with a range of physical properties and macromolecular architectures, and with multiple functional handles to allow derivatisation with 'actives' for sensing or therapy. Here we describe the syntheses of amphiphilic tri-and tetra-block copolymers, using diazabicyclo[5.4.0]undec-5-ene (DBU) as a metal-free catalyst for ring-opening polymerisations of the widely-utilised monomer lactide combined with a functionalised protected cyclic carbonate. These syntheses employed PEGylated macroinitiators with varying chain lengths and architectures, as well as a labile-ester methacrylate initiator, and produced block copolymers with good control over monomer incorporation, molar masses, side-chain and terminal functionality and physico-chemical properties. Regardless of the nature of the initiators, the fidelity of the hydroxyl end group was maintained as confirmed by a second ROP chain extension step, and polymers with acryloyl/methacryloyl termini were able to undergo a second tandem reaction step, in particular thiol-ene click and RAFT polymerisations for the production of hyperbranched materials. Furthermore, the polymer side-chain functionalities could be easily deprotected to yield an active amine which could be subsequently coupled to a drug molecule in good yields. The resultant amphiphilic copolymers formed a range of unimolecular or kinetically-trapped micellar-like nanoparticles in aqueous environments, and the non-cationic polymers were all well-tolerated by MCF-7 breast cancer cells. The rapid and facile route to such highly adaptable polymers, as demonstrated here, offers promise for a range of bio materials applications.

Citation

Vasey, C. E., Pearce, A. K., Sodano, F., Cavanagh, R., Abelha, T., Cuzzucoli Crucitti, V., Anane-Adjei, A. B., Ashford, M., Gellert, P., Taresco, V., & Alexander, C. (2019). Amphiphilic tri- and tetra-block co-polymers combining versatile functionality with facile assembly into cytocompatible nanoparticles. Biomaterials Science, 7(9), 3832-3845. https://doi.org/10.1039/c9bm00667b

• Journal Article Type: Article
• Acceptance Date: May 22, 2019
• Publication Date: Jul 9, 2019
• Deposit Date: May 24, 2019
• Publicly Available Date: Jul 10, 2020
• Journal: Biomaterials Science
• Electronic ISSN: 2047-4830
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 9
• Pages: 3832-3845
• DOI: https://doi.org/10.1039/c9bm00667b
• Keywords: General Materials Science; Biomedical Engineering
• Public URL: https://nottingham-repository.worktribe.com/output/2089680
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2019/BM/C9BM00667B#!divAbstract
• Additional Information: : This document is Similarity Check deposited; : Supplementary Information; : Amanda K. Pearce (ORCID); : Marianne Ashford (ORCID); : Vincenzo Taresco (ORCID); : Cameron Alexander (ORCID); : Cameron Alexander (ResearcherID); : Single-blind; : Received 26 April 2019; Accepted 22 May 2019; Advance Article published 9 July 2019; Version of Record published 20 August 2019
• Contract Date: May 24, 2019