Liquid Droplet Formation and Facile Cytosolic Translocation of IgG in the Presence of Attenuated Cationic Amphiphilic Lytic Peptides

Angew Chem Int Ed Engl. 2021 Sep 1;60(36):19804-19812. doi: 10.1002/anie.202105527. Epub 2021 Jul 9.


Fc region binding peptide conjugated with attenuated cationic amphiphilic lytic peptide L17E trimer [FcB(L17E)3 ] was designed for immunoglobulin G (IgG) delivery into cells. Particle-like liquid droplets were generated by mixing Alexa Fluor 488 labeled IgG (Alexa488-IgG) with FcB(L17E)3 . Droplet contact with the cellular membrane led to spontaneous influx and distribution of Alexa488-IgG throughout cells in serum containing medium. Involvement of cellular machinery accompanied by actin polymerization and membrane ruffling was suggested for the translocation. Alexa488-IgG negative charges were crucial in liquid droplet formation with positively charged FcB(L17E)3 . Binding of IgG to FcB(L17E)3 may not be necessary. Successful intracellular delivery of Alexa Fluor 594-labeled anti-nuclear pore complex antibody and anti-mCherry-nanobody tagged with supernegatively charged green fluorescence protein allowed binding to cellular targets in the presence of FcB(L17E)3 .

Keywords: antibodies; intracellular delivery; liquid droplet; liquid-liquid phase separation (LLPS); peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations / chemistry
  • Cations / metabolism
  • Cytosol / chemistry
  • Cytosol / metabolism*
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / metabolism*
  • Molecular Structure
  • Particle Size
  • Peptides / chemistry
  • Peptides / metabolism*
  • Surface-Active Agents / chemistry
  • Surface-Active Agents / metabolism*


  • Cations
  • Immunoglobulin G
  • Peptides
  • Surface-Active Agents