Promoting Multivalent Antibody-Antigen Interactions by Tethering Antibody Molecules on a PEGylated Dendrimer-Supported Lipid Bilayer

Biomacromolecules. 2018 Feb 12;19(2):426-437. doi: 10.1021/acs.biomac.7b01515. Epub 2018 Jan 11.

Abstract

To efficiently isolate maximal quantity of circulating tumor cells (CTCs) and circulating tumor cell microembolis (CTMs) from patient blood by antibody coated microfluidics, a multifunctional, pegylated polyamidoamine-dendrimers conjugated supported lipid bilayer surface construct was proposed to enhance accessibility of antibody molecules to the antigen molecules on target CTCs. The combination of a hydrated, stretchable dendrimer and a laterally mobile supported lipid bilayer (SLB) provide attached antibody molecules with 2.5-dimensional chain movement, achieving multivalency between the surface antibody and cell antigen molecules. An over 170% enhancement is distinctive for Panc-1 cells that expresses low antigen level. Of seven pancreatic ductal adenocarcinoma patients, an average 440 single CTCs and 90 CTMs were collected in 2 mL of peripheral blood, which were 1.6 times and 2.3 times more, than those captured by the SLB-only microfluidics. In summary, we have demonstrated a material design to enhance multivalent antibody-antigen interaction, which is useful for rare cell enrichment and cancer detection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Antibodies / chemistry
  • Antibodies / immunology*
  • Antibodies, Immobilized / chemistry
  • Antibodies, Immobilized / immunology*
  • Antigen-Antibody Complex / chemistry
  • Antigen-Antibody Complex / immunology*
  • Dendrimers / chemistry*
  • HCT116 Cells
  • Humans
  • Lipid Bilayers / chemistry*
  • Microfluidics / methods
  • Neoplastic Cells, Circulating / immunology*
  • Pancreatic Neoplasms / blood
  • Polyethylene Glycols / chemistry

Substances

  • Antibodies
  • Antibodies, Immobilized
  • Antigen-Antibody Complex
  • Dendrimers
  • Lipid Bilayers
  • PAMAM Starburst
  • Polyethylene Glycols