Utilizing the Hofmeister Effect to Induce Hydrogelation of Nonionic Supramolecular Polymers into a Therapeutic Depot
Utilizing the Hofmeister Effect to Induce Hydrogelation of Nonionic Supramolecular Polymers into a Therapeutic Depot
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DOI：
10.1002/anie.202306652
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发表时间：
2023-09-14
影响因子：
16.6
通讯作者：
Cui，Honggang
中科院分区：
文献类型：
--
作者：
Wang，Han;Su，Hao;Cui，Honggang
非离子水凝胶由于其相对于其带电对应物的最小免疫原性而对于长期治疗性植入特别感兴趣。然而，在生理条件下原位形成非离子型超分子水凝胶一直是一项具有挑战性的任务。在这种情况下，我们报告了我们发现的盐触发的非离子超分子聚合物（SP）通过Hofmeister效应自组装前药水凝胶因子（SAPH）形成的水凝胶化。所设计的SAPH由两个SN-38单元（抗癌药物伊立替康的活性代谢物）和一个接枝有两个或四个寡聚乙二醇（OEG）片段的短肽组成。在水中自组装后，所得的非离子SP可以在添加磷酸盐后触发凝胶化。我们的1H NMR研究表明，添加的磷酸盐导致亚甲基质子的化学位移发生变化，这表明水-醚氢键的破坏以及随后SPs周围水化壳的重组。这种去屏蔽效应与添加的盐的量相称，可能促进SAPH细丝之间的缔合相互作用以渗透到3D网络中。所形成的水凝胶表现出SN-38水凝胶剂的持续释放特性，其对癌细胞有效。
Nonionic hydrogels are of particular interest for long‐term therapeutic implantation due to their minimal immunogenicity relative to their charged counterparts. However, in situ formation of nonionic supramolecular hydrogels under physiological conditions has been a challenging task. In this context, we report on our discovery of salt‐triggered hydrogelation of nonionic supramolecular polymers (SPs) formed by self‐assembling prodrug hydrogelators (SAPHs) through the Hofmeister effect. The designed SAPHs consist of two SN‐38 units, which is an active metabolite of the anticancer drug irinotecan, and a short peptide grafted with two or four oligoethylene glycol (OEG) segments. Upon self‐assembly in water, the resultant nonionic SPs can be triggered to gel upon addition of phosphate salts. Our1H NMR studies revealed that the added phosphates led to a change in the chemical shift of the methylene protons, suggestive of a disruption of the water‐ether hydrogen bonds and consequent reorganization of the hydration shell surrounding the SPs. This deshielding effect, commensurate with the amount of salt added, likely promoted associative interactions among the SAPH filaments to percolate into a 3D network. The formed hydrogels exhibited a sustained release profile of SN‐38 hydrogelator that acted potently against cancer cells.