3 years ago

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
Hai Xu, Yurong Zhao, Zhe Hou, Xuejing Cui, Yu Zhang, Cuixia Chen
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.

Publisher URL: http://dx.doi.org/10.1021/acs.biomac.7b00911

DOI: 10.1021/acs.biomac.7b00911

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