Protein-Antibody Conjugates (PACs): A Plug-and-Play Strategy for Covalent Conjugation and Targeted Intracellular Delivery of Pristine Proteins

Angew Chem Int Ed Engl. 2021 Jun 1;60(23):12813-12818. doi: 10.1002/anie.202103106. Epub 2021 May 5.

Abstract

We report here on protein-antibody conjugates (PACs) that are used for antibody-directed delivery of protein therapeutics to specific cells. PACs have the potential to judiciously combine the merits of two prolific therapeutic approaches-biologics and antibody-drug conjugates. We utilize spherical polymer brushes to construct PACs using the combination of two simple and efficient functionally orthogonal click chemistries. In addition to the synthesis and characterization of these nanoparticles, we demonstrate that PACs are indeed capable of specifically targeting cells based on the presence of target antigen on the cell surface to deliver proteins. The potentially broad adaptability of PACs opens up new opportunities for targeted biologics in therapeutics and sensing.

Keywords: antibody-targeted delivery; click chemistry; drug delivery; protein encapsulation; protein-antibody conjugates.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies / chemistry*
  • Cell Line, Tumor
  • Fullerenes / chemistry*
  • Humans
  • Nanoparticles / chemistry
  • Particle Size
  • Receptor, ErbB-2 / chemistry*

Substances

  • Antibodies
  • Fullerenes
  • pristine (C60)
  • ERBB2 protein, human
  • Receptor, ErbB-2