A multifunctional drug delivery system based on switchable peptide-stabilized emulsions

Daniel Boas, Alexander van Teijlingen, Zohar Shpilt, Deborah E. Shalev*, Edit Y. Tshuva*, Tell Tuttle*, Meital Reches*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Emulsions are commonly used for drug delivery, yet they are usually limited to exclusively delivering either lipophilic or hydrophilic compounds. This separation negates possible synergetic therapeutic roles between such compounds. Here, we introduce a design for a short peptide that can stabilize emulsions. Upon binding certain metal ions, the peptide acts as a molecular switch, changes conformation, and becomes amphiphilic. Spectroscopic methods, NMR, and molecular dynamics provide information on the mechanism of this complexation-triggered amphiphilicity. The stability of these unique emulsions is based on histidine-metal bonds, which break at low pH values, selectively releasing their contents at the extracellular pH of tumors. Paclitaxel-encapsulated emulsion demonstrates strong activity against HeLa cells with an IC50 of 70 nM, possibly enhanced by the simultaneous release of Zn2+ ions. Importantly, the emulsion is easily functionalized with various hexahistidine-tagged motifs that can supply the emulsion with many functions beyond drug delivery.

Original languageAmerican English
StateAccepted/In press - 2024

Bibliographical note

Publisher Copyright:
© 2024 Elsevier Inc.


  • amphiphilic peptides
  • drug delivery
  • emulsion functionalization
  • metal-binding peptides
  • peptide-stabilized emulsions
  • SDG3: Good health and well-being


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