{"title":"Harnessing the hydrolytic stability of poly(2-oxazine) living chain-ends for direct aqueous bioconjugations","authors":"Niccolò Lusiani, Ondrej Sedlacek","doi":"10.1016/j.eurpolymj.2025.113842","DOIUrl":null,"url":null,"abstract":"<div><div>Poly(2-oxazine)s (PAOzi) have recently emerged as attractive alternatives to poly(2-oxazoline)s (PAOx) for biomedical applications. In this work, we exploit the slower hydrolysis of the oxazinium chain-ends in PAOzi, synthesized by cationic ring-opening polymerization, enabling direct, one-step nucleophilic conjugation with amines in aqueous environments. On the other hand, analogous PAOx showed exclusively chain-end hydrolysis. We show that the PAOzi hydrolysis rate strongly depends on pH, guiding us to optimal conjugation conditions. By employing buffer/DMSO mixtures and precisely tuning pH, we achieved good conjugation efficiencies with model primary amine and bovine serum albumin (BSA). Efficient bioconjugation under these mild, biocompatible conditions was confirmed by MALDI-TOF mass spectrometry, SEC, and diffusion-ordered (DOSY) NMR. Such aqueous conjugation is unique for living polymers arising from ionic polymerizations, which are notoriously known for their moisture sensitivity. This streamlined, scalable approach offers a versatile platform for next-generation polymer-protein conjugates and advanced drug delivery systems.</div></div>","PeriodicalId":315,"journal":{"name":"European Polymer Journal","volume":"228 ","pages":"Article 113842"},"PeriodicalIF":5.8000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Polymer Journal","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014305725001302","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"POLYMER SCIENCE","Score":null,"Total":0}
引用次数: 0
Abstract
Poly(2-oxazine)s (PAOzi) have recently emerged as attractive alternatives to poly(2-oxazoline)s (PAOx) for biomedical applications. In this work, we exploit the slower hydrolysis of the oxazinium chain-ends in PAOzi, synthesized by cationic ring-opening polymerization, enabling direct, one-step nucleophilic conjugation with amines in aqueous environments. On the other hand, analogous PAOx showed exclusively chain-end hydrolysis. We show that the PAOzi hydrolysis rate strongly depends on pH, guiding us to optimal conjugation conditions. By employing buffer/DMSO mixtures and precisely tuning pH, we achieved good conjugation efficiencies with model primary amine and bovine serum albumin (BSA). Efficient bioconjugation under these mild, biocompatible conditions was confirmed by MALDI-TOF mass spectrometry, SEC, and diffusion-ordered (DOSY) NMR. Such aqueous conjugation is unique for living polymers arising from ionic polymerizations, which are notoriously known for their moisture sensitivity. This streamlined, scalable approach offers a versatile platform for next-generation polymer-protein conjugates and advanced drug delivery systems.
期刊介绍:
European Polymer Journal is dedicated to publishing work on fundamental and applied polymer chemistry and macromolecular materials. The journal covers all aspects of polymer synthesis, including polymerization mechanisms and chemical functional transformations, with a focus on novel polymers and the relationships between molecular structure and polymer properties. In addition, we welcome submissions on bio-based or renewable polymers, stimuli-responsive systems and polymer bio-hybrids. European Polymer Journal also publishes research on the biomedical application of polymers, including drug delivery and regenerative medicine. The main scope is covered but not limited to the following core research areas:
Polymer synthesis and functionalization
• Novel synthetic routes for polymerization, functional modification, controlled/living polymerization and precision polymers.
Stimuli-responsive polymers
• Including shape memory and self-healing polymers.
Supramolecular polymers and self-assembly
• Molecular recognition and higher order polymer structures.
Renewable and sustainable polymers
• Bio-based, biodegradable and anti-microbial polymers and polymeric bio-nanocomposites.
Polymers at interfaces and surfaces
• Chemistry and engineering of surfaces with biological relevance, including patterning, antifouling polymers and polymers for membrane applications.
Biomedical applications and nanomedicine
• Polymers for regenerative medicine, drug delivery molecular release and gene therapy
The scope of European Polymer Journal no longer includes Polymer Physics.