Abstract：
External stimuli-responsive DNA hydrogels present interesting platforms for drug loading and triggered release. Typically, drug molecules are encapsulated within three-dimensionally hybridized DNA networks. However, the utilization of drug molecules as cofactors to facilitate the directed assembly of DNA strands into hydrogel frameworks and their subsequent controlled release remains to be explored. Herein, we introduce the guided assembly of oligo-adenine (A-strand) into an acidic pH-responsive DNA hydrogel using an anticancer drug, coralyne (COR), as a low-molecular-weight cofactor. At pH 7, COR orchestrates the assembly of A-strand into an antiparallel duplex configuration cross-linked by A-COR-A units at a stoichiometric ratio of one COR cofactor per four adenine bases, resulting in a DNA hydrogel characterized by A-COR-A duplex bridges. At pH 4-5, the instability of A-COR-A units results in the disintegration of the duplex into its constituent components, leading to the release of COR and simultaneous dissociation of the DNA hydrogel matrix. This study introduces a method by which drug molecules, exemplified here by COR, facilitate the direct formation of a supramolecular cofactor-DNA complex, subsequently leading to the creation of a stimuli-responsive DNA hydrogel. This approach may inspire future investigations into DNA hydrogels tailored for controlled drug encapsulation and release applications.
摘要：
外部刺激响应性DNA水凝胶为药物加载和触发释放提供了有趣的平台。通常,药物分子被封装在三维杂交的DNA网络中。然而,利用药物分子作为辅因子来促进DNA链定向组装成水凝胶框架及其随后的受控释放仍有待探索。在这里，我们使用抗癌药物将寡腺嘌呤（A链）引导组装到酸性pH响应性DNA水凝胶中，coralyne(COR),作为低分子量辅因子。在pH7时，COR将A链组装成由A-COR-A单元交联的反平行双链体构型，化学计量比为每四个腺嘌呤碱基一个COR辅因子，产生以A-COR-A双链桥为特征的DNA水凝胶。在pH4-5时，A-COR-A单元的不稳定性导致双链体分解为其组成成分，导致COR的释放和DNA水凝胶基质的同时解离。这项研究介绍了一种方法，药物分子，这里以COR为例，促进超分子辅因子-DNA复合物的直接形成，随后导致产生刺激响应性DNA水凝胶。这种方法可能会激发未来对DNA水凝胶的研究，这些水凝胶是为受控药物封装和释放应用而定制的。
