Surface protein engineering increases the circulation time of a cell membrane-based nanotherapeutic

Nanomedicine. 2019 Jun;18:169-178. doi: 10.1016/j.nano.2019.02.024. Epub 2019 Mar 8.

Abstract

Mammalian cell membranes are often incompatible with chemical modifications typically used to increase circulation half-life. Using cellular nanoghosts as a model, we show that proline-alanine-serine (PAS) peptide sequences expressed on the membrane surface can extend the circulation time of a cell membrane derived nanotherapeutic. Membrane expression of a PAS 40 repeat sequence decreased protein binding and resulted in a 90% decrease in macrophage uptake when compared with non-PASylated controls (P ≤ 0.05). PASylation also extended circulation half-life (t1/2 = 37 h) compared with non-PASylated controls (t1/2 = 10.5 h) (P ≤ 0.005), resulting in ~7-fold higher in vivo serum concentrations at 24 h and 48 h (P ≤ 0.005). Genetically engineered membrane expression of PAS repeats may offer an alternative to PEGylation and provide extended circulation times for cellular membrane-derived nanotherapeutics.

Keywords: Cell ghosts; Drug delivery; Lipid-polymer hybrid nanoparticles; Nanoghosts; Nanomedicine; PASylation; Synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Animals
  • Blood Proteins / metabolism
  • Cell Membrane / metabolism*
  • Dynamic Light Scattering
  • HEK293 Cells
  • Humans
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Nanoparticles / ultrastructure
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Protein Engineering*
  • Rats
  • Surface Properties
  • Tissue Distribution

Substances

  • Blood Proteins
  • Polylactic Acid-Polyglycolic Acid Copolymer