It is known that guanosine derivatives (G) self-assemble in water forming long, flexible, and interacting aggregates (the so-called G-quadruplexes): by modulating the quadruplex charges, e.g. simply using a mixture of guanosine 5′-monophosphate (GMP) and guanosine (Gua), multi-responsive, self-healing hydrogels can be obtained. In this paper, the potential application of G-hydrogels as drug delivery systems has been assessed. Hydrogels were prepared at different Gua:GMP molar ratios. The photosensitizer Methylene Blue and the pro-apoptotic protein cytochrome C were used as cargo molecules. Small angle x-ray scattering and atomic force microscopy experiments confirmed the presence of G-quadruplexes disposed in swollen matrices with different mesh-sizes. Rheology measurements showed that the Gua:GMP molar ratio leads to specific drug release mechanisms, as the gel strength is finely tuned by electrostatic repulsion and van der Waals attraction between G-quadruplexes. Noteworthy, the gel cohesion and the drug release were pH responsive. Swelling, self-healing and cell viability features were also investigated: the results qualify the Gua:GMP hydrogel as an excellent biomaterial that can entrap and deliver key biomolecules in a sustained and responsive release manner.

已知鸟苷衍生物（G）在水中自组装形成长的，柔性的和相互作用的聚集体（所谓的G-四链体）：通过调节四链体电荷，例如简单地使用鸟苷5'-单磷酸酯的混合物（ GMP）和鸟苷（Gua），可以获得多反应性，自愈的水凝胶。在本文中，已经评估了G-水凝胶作为药物递送系统的潜在应用。以不同的Gua：GMP摩尔比制备水凝胶。光敏剂亚甲基蓝和促凋亡蛋白细胞色素C被用作货物分子。小角度X射线散射和原子力显微镜实验证实，存在于具有不同筛孔尺寸的溶胀基质中的G四联体存在。流变学测量表明，刮a：GMP摩尔比可导致特定的药物释放机制，因为凝胶强度可通过G-四链体之间的静电排斥和范德华力吸引进行微调。值得注意的是，凝胶内聚力和药物释放是pH响应的。还研究了肿胀，自我修复和细胞生存能力：结果证明Gua：GMP水凝胶是一种优秀的生物材料，可以持续和响应性释放的方式截留和递送关键生物分子。