Alternatives for strain-promoted azide-alkyne cycloaddition (SPAAC) chemistries are needed because of the employment of expensive and not easily scalable precursors such as bicyclo[6.1.0]non-4-yne (BCN). Inverse electron demand Diels Alder (iEDDA)-based click chemistries, using dienophiles and tetrazines, offer a more bioorthogonal and faster toolbox, especially in the biomedical field. Here, the straightforward synthesis of dendritic polyglycerin dienophiles (dPG-dienophiles) and dPG-methyl-tetrazine (dPG-metTet) as macromonomers for a fast, stable, and scalable nanogel formation by inverse nanoprecipitation is reported. Nanogel size-influencing parameters are screened such as macromonomer concentration and water-to-acetone ratio are screened. dPG-norbonene and dPG-cyclopropene show fast and stable nanogel formation in the size range of 40-200 nm and are thus used for the coprecipitation of the model protein myoglobin. High encapsulation efficiencies of more than 70% at a 5 wt% feed ratio are obtained in both cases, showing the suitability of the mild gelation chemistry for the encapsulation of small proteins.

中文翻译：

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系统筛选不同的基于甘油的双亲大分子单体，通过IEDDA逆纳米沉淀法有效形成纳米凝胶。

由于使用了昂贵且不易扩展的前体，例如双环[6.1.0] non-4-yne（BCN），因此需要使用应变促进的叠氮化物-炔烃环加成（SPAAC）化学方法的替代品。反向电子需求基于Diels Alder（iEDDA）的点击化学，使用亲二烯体和四嗪，提供了更正交的生物和更快的工具箱，尤其是在生物医学领域。在此，报道了通过逆纳米沉淀法快速，稳定，可扩展地形成纳米凝胶的树状聚甘油二烯亲和体（dPG-亲二烯体）和dPG-甲基四嗪（dPG-metTet）作为大分子单体的直接合成方法。筛选影响纳米凝胶尺寸的参数，例如大分子单体浓度和水与丙酮的比例。dPG-降冰片烯和dPG-环丙烯在40-200 nm的尺寸范围内显示出快速稳定的纳米凝胶形成，因此可用于模型蛋白肌红蛋白的共沉淀。在两种情况下，进料比为5重量％时，封装效率都超过70％，这表明温和的凝胶化学方法适用于小蛋白的封装。