Rational Design of Short Peptide-Based Hydrogels with MMP-2 Responsiveness for Controlled Anticancer Peptide Delivery
Rational Design of Short Peptide-Based Hydrogels with MMP-2 Responsiveness for Controlled Anticancer Peptide Delivery
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具有 MMP-2 响应性的短肽水凝胶的合理设计用于受控抗癌肽递送
DOI：
10.1021/acs.biomac.7b00911
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发表时间：
2017-11-01
影响因子：
6.2
通讯作者：
Xu, Hai
中科院分区：
文献类型：
--
作者：
Chen, Cuixia;Zhang, Yu;Xu, Hai
分子自组装使得通过初始分子设计来控制先进材料的结构和性能成为可能。为了开发具有刺激响应性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工程化为自组装肽序列来设计短的两亲性肽。我们证明，设计的Ac-I（3）SLKG-NH 2和Ac-I（3）SLGK-NH 2自组装成纤维状水凝胶，并且Ac-I（3）SLKG-NH 2水凝胶显示出响应于MMP-2的降解，但Ac-I（3）SLGK-NH 2水凝胶没有。发现Ac-I（3）SLKG-NH 2裂解成Ac-I3 S和LKG-NH 2是酶促降解的机理。最后，当抗癌肽G（IIKK）（3）I-NH 2（G3）包埋到Ac-I（3）SLKG-NH 2水凝胶中时，在过表达MMP-2的HeLa细胞存在下，其释放以“细胞需要”的方式发生，因此导致对它们在凝胶上生长的显著抑制作用。
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-I(3)SLKG-NH2 and Ac-I(3)SLGK-NH2 self-assembled into fibrillar hydrogels and that the Ac-I(3)SLKG-NH2 hydrogel showed degradation in response to MMP-2 but the Ac-I(3)SLGK-NH2 hydrogel did not. The cleavage of Ac-I(3)SLKG-NH2 into Ac-I3S and LKG-NH2 was found to be mechanistically responsible for the enzymatic degradation. Finally, when an anticancer peptide G(IIKK)(3)I-NH2 (G3) was entrapped into Ac-I(3)SLKG-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.