Self-assembly of polyphosphazene immunoadjuvant with poly(ethylene oxide) enables advanced nanoscale delivery modalities and regulated pH-dependent cellular membrane activity.
Self-assembly of polyphosphazene immunoadjuvant with poly(ethylene oxide) enables advanced nanoscale delivery modalities and regulated pH-dependent cellular membrane activity.
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DOI：
10.1016/j.heliyon.2016.e00102
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发表时间：
2016-04
期刊：
影响因子：
4
通讯作者：
Fuerst TR
中科院分区：
文献类型：
--
作者：
Andrianov AK;Marin A;Fuerst TR
水溶性聚磷腈多酸，如聚[二（羧基苯氧基）磷腈]（PCPP），由于其独特的免疫佐剂和疫苗递送性质而受到极大关注。我们报告说，PCPP可以在中性pH值的水溶液中通过建立氢键自发地与常见的制剂辅料-聚醚自组装成分子间复合物。所得到的先进的PCPP递送方式可以从纳米级的大分子组装体到物理交联的水凝胶，并且可以通过改变聚合物比率和聚醚的分子量来调节物理状态。已经证明，这种大分子复合物保持蛋白质结合能力-这是递送系统的关键特征。重要的是，用聚醚对PCPP免疫佐剂的非共价修饰引入了pH依赖性膜破坏活性，这不是PCPP本身的特征，并且通常与大分子载体促进内体逃逸的能力相关。这可能会影响免疫佐剂的作用机制显示的PCPP，提供手段，其微调，以及提供重要的见解，了解基本的物理化学特性的聚磷腈免疫佐剂和它们的体内活性之间的关系。
Water-soluble polyphosphazene polyacids, such as poly[di(carboxylatophenoxy)phosphazene] (PCPP), have been of significant interest due to their unique immunoadjuvant and vaccine delivery properties. We report that PCPP can spontaneously self-assemble into intermolecular complexes with common formulation excipients − polyethers in aqueous solutions at neutral pH through the establishment of hydrogen bonds. The resulting advanced PCPP delivery modalities can range from macromolecular assemblies at the nanoscale level to physically cross-linked hydrogels and the physical state can be modulated through varying polymer ratios and molecular weight of polyether. It has been demonstrated that such macromolecular complexes maintain protein-binding ability − a key characteristics of the delivery system. Importantly, the non-covalent modification of PCPP immunoadjuvant with polyethers introduces pH dependent membrane disruptive activity, which is not characteristic for PCPP itself, and is typically correlated to the ability of macromolecular carrier to facilitate endosomal escape. This can potentially affect the mechanism of immunoadjuvant action displayed by PCPP, afford means for its fine-tuning, as well as provide important insights for understanding the relationship between fundamental physico-chemical characteristics of polyphosphazene immunoadjuvants and their activity in vivo.