Synthesis of Passerini-3CR Polymers and Assembly into Cytocompatible Polymersomes

Travanut, Alessandra; Monteiro, Patr�cia F.; Oelmann, Stefan; Howdle, Steven M.; Grabowska, Anna M.; Clarke, Philip A.; Ritchie, Alison A.; Meier, Michael A.R.; Alexander, Cameron

Abstract

© 2020 The Authors. Published by Wiley-VCH GmbH The versatility of the Passerini three component reaction (Passerini-3CR) is herein exploited for the synthesis of an amphiphilic diblock copolymer, which self-assembles into polymersomes. Carboxy-functionalized poly(ethylene glycol) methyl ether is reacted with AB-type bifunctional monomers and tert-butyl isocyanide in a single process via Passerini-3CR. The resultant diblock copolymer (P1) is obtained in good yield and molar mass dispersity and is well tolerated in model cell lines. The Passerini-3CR versatility and reproducibility are shown by the synthesis of P2, P3, and P4 copolymers. The ability of the Passerini P1 polymersomes to incorporate hydrophilic molecules is verified by loading doxorubicin hydrochloride in P1DOX polymersomes. The flexibility of the synthesis is further demonstrated by simple post-functionalization with a dye, Cyanine-5 (Cy5). The obtained P1-Cy5 polymersomes rapidly internalize in 2D cell monolayers and penetrate deep into 3D spheroids of MDA-MB-231 triple-negative breast cancer cells. P1-Cy5 polymersomes injected systemically in healthy mice are well tolerated and no visible adverse effects are seen under the conditions tested. These data demonstrate that new, biodegradable, biocompatible polymersomes having properties suitable for future use in drug delivery can be easily synthesized by the Passerini-3CR.

Citation

Travanut, A., Monteiro, P. F., Oelmann, S., Howdle, S. M., Grabowska, A. M., Clarke, P. A., …Alexander, C. (2021). Synthesis of Passerini-3CR Polymers and Assembly into Cytocompatible Polymersomes. Macromolecular Rapid Communications, 42(6), Article 2000321. https://doi.org/10.1002/marc.202000321

• Journal Article Type: Article
• Acceptance Date: Jul 27, 2020
• Online Publication Date: Aug 16, 2020
• Publication Date: 2021-03
• Deposit Date: Jul 29, 2020
• Publicly Available Date: Aug 17, 2021
• Journal: Macromolecular Rapid Communications
• Print ISSN: 1022-1336
• Electronic ISSN: 1521-3927
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 42
• Issue: 6
• Article Number: 2000321
• DOI: https://doi.org/10.1002/marc.202000321
• Public URL: https://nottingham-repository.worktribe.com/output/4794458
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1002/marc.202000321