Molecular self-assembly makes it feasible to harness the structures and properties of advanced materials via initial molecular design. To develop short peptide-based hydrogels with stimuli responsiveness, we designed here short amphiphilic peptides by engineering protease cleavage site motifs into self-assembling peptide sequences. We demonstrated that the designed Ac-I₃SLKG-NH₂ and Ac-I₃SLGK-NH₂ self-assembled into fibrillar hydrogels and that the Ac-I₃SLKG-NH₂ hydrogel showed degradation in response to MMP-2 but the Ac-I₃SLGK-NH₂ hydrogel did not. The cleavage of Ac-I₃SLKG-NH₂ into Ac-I₃S and LKG-NH₂ was found to be mechanistically responsible for the enzymatic degradation. Finally, when an anticancer peptide G(IIKK)₃I-NH₂ (G3) was entrapped into Ac-I₃SLKG-NH₂ hydrogels, its release was revealed to occur in a “cell-demanded” way in the presence of HeLa cells that overexpress MMP-2, therefore leading to a marked inhibitory effect on their growth on the gels.

中文翻译：

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具有MMP-2响应能力的短肽基水凝胶可控抗癌肽传递的合理设计

分子自组装使得通过初始分子设计利用先进材料的结构和性能成为可能。为了开发具有刺激响应能力的基于短肽的水凝胶，我们在这里通过将蛋白酶切割位点基序改造成自组装肽序列来设计短两亲性肽。我们证明设计的Ac-I ₃ SLKG-NH ₂和Ac-I ₃ SLGK-NH ₂自组装为原纤维水凝胶，并且Ac-I ₃ SLKG-NH ₂水凝胶显示出对MMP-2的降解，但AC-I ₃ SLGK-NH ₂凝胶没有。Ac-I ₃ SLKG-NH ₂的裂解发现向Ac- 1S ₃ S和LKG-NH _2的转化是机械上导致酶促降解的原因。最后，当抗癌肽G（IIKK）₃ I-NH ₂（G3）中的溶液包埋到AC-I ₃ SLKG-NH _2倍的水凝胶，其释放显露在“细胞要求”的方式发生在HeLa的存在过表达MMP-2的细胞会因此对其在凝胶上的生长产生明显的抑制作用。