Artificial peptide-controlled protein release of Zn2+-triggered, self-assembled histidine-tagged protein microparticle

Tzu Yin Chen, Wan Jung Cheng, Jia Cherng Horng, Hsin Yun Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Protein microparticles have received attention as drug delivery systems because of their high protein stability and prolonged release in vivo. However, most current preparation processes introduce chemical crosslinkers, which often lead to protein inactivation and limit drug efficacy in delivery systems. In this study, we employed the well-known hexahistidine (His)-tag recombinant protein technology and a metal-triggerable collagen-mimetic peptide to enhance the binding strength between the protein and metal ion and fine-tuned the protein drug release. His-tagged proteins self-assembled to form microparticles (∼2 μm) upon zinc ion treatment and sustained protein drug release was achieved in physiological saline. The results also indicated that by adjusting the peptide concentration and N- and C-terminal hexahistidine-tags, protein release could be controlled. Moreover, no protein denaturation was observed. We developed a universal strategy for facile protein microparticle fabrication under mild conditions and we demonstrated its potential as a therapeutics formulation with tunable protein release.

Original languageEnglish
Article number110644
JournalColloids and Surfaces B: Biointerfaces
StatePublished - Mar 2020


  • Collagen-Mimetic
  • His-tag
  • Metal-Induced self-assembly
  • Peptide
  • Protein microparticle


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