Synthesis of Passerini‐3CR Polymers and Assembly into Cytocompatible Polymersomes. Issue 6 (16th August 2020)

• Record Type: Journal Article
• Authors: Travanut, Alessandra; Monteiro, Patrícia F.; Oelmann, Stefan; Howdle, Steven M.; Grabowska, Anna M.; Clarke, Philip A.; Ritchie, Alison A.; Meier, Michael A. R.; Alexander, Cameron
• Other Names: Meier Michael A. R. guestEditor.; Hu Rongrong guestEditor.; Tang Ben Zhong guestEditor.
• Is Part Of: Macromolecular rapid communications. Volume 42:Issue 6(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-16
• Subjects: drug delivery -- multicomponent reactions -- Passerini‐3CR -- polymersomes; Macromolecules -- Periodicals; Polymers -- Periodicals; Chemistry -- Periodicals; 547.705
• DOI: 10.1002/marc.202000321
• Languages: English
• ISSNs: 1022-1336

Abstract

Abstract: 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. Abstract : A facile, versatile and reproducible synthesis via the Passerini three component reaction (Passerini‐3CR) of amphiphilic copolymers, which self‐assemble into polymersomes is herein shown. These materials are rapidly internalized by breast cells, are cytocompatible and are well tolerated in healthy mice. This new route to polymersomes demonstrates the versatility of the Passerini‐3CR for new drug delivery systems which have properties advantageous for clinical translation.