Supramolecular β-Sheets Stabilized Protein Nanocarriers for Drug Delivery and Gene Transfection

Yuan Ping, Dawei Ding, Ricardo A.N.S. Ramos, Harini Mohanram, Kanagavel Deepankumar, Jianqing Gao, Guping Tang, Ali Miserez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Suckerin proteins, recently discovered in the sucker ring teeth of squids, represent a family of promising structural biomacromolecules that can form supramolecular networks stabilized by nanoconfined β-sheets. Exploiting this feature as well as their specific amino acid composition, we demonstrate that artificial suckerin-19 (S-19) can be engineered into nanocarriers for efficient drug delivery and gene transfection in vitro and in vivo. First, we demonstrate that S-19 self-assembles into β-sheet stabilized nanoparticles with controlled particle sizes of 100-200 nm that are able to encapsulate hydrophobic drugs for pH-dependent release in vitro, and that can effectively inhibit tumor growth in vivo. We also show that S-19 can complex and stabilize plasmid DNA, with the complexes stabilized by hydrophobic interactions of the β-sheet domains as opposed to electrostatic interactions commonly achieved with cationic polymers, thus lowering cytotoxicity. The elevated Histidine content of S-19 appears critical to trigger endosomal escape by the proton sponge effect, thereby ensuring efficient gene transfection both in vitro and in vivo. Our study demonstrates that S-19 represents a promising functional protein nanocarrier that could be used for various drug and gene delivery applications.

Original languageEnglish
Pages (from-to)4528-4541
Number of pages14
JournalACS Nano
Volume11
Issue number5
DOIs
Publication statusPublished - 23 May 2017
Externally publishedYes

Keywords

  • chemotherapy
  • gene therapy
  • histidine-rich protein
  • nanomedicine
  • protein nanoparticle

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