Remarkably size-regulated cell invasion by artificial viruses. Saccharide-dependent self-aggregation of glycoviruses and its consequences in glycoviral gene delivery

J Am Chem Soc. 2003 Jul 16;125(28):8465-75. doi: 10.1021/ja035636f.

Abstract

We here report a novel example of artificial glycoviral vectors constructed via number- and size-controlled gene (pCMVluc, 7040 bp) coating with micellar glycocluster nanoparticles (GNPs) of calix[4]resorcarene-based macrocyclic glycocluster amphiphiles having eight or five saccharide moieties with terminal alpha-glucose (alpha-Glc), beta-glucose (beta-Glc), or beta-galactose (beta-Gal) residues. The resulting glycoviruses are compactly packed (approximately 50 nm) and well charge-shielded (zeta approximately equal 0 mV), undergo saccharide-dependent (alpha-Glc > beta-Gal >> beta-Glc) self-aggregation, and transfect cell (Hela and HepG2) cultures as triggered by the pinocytic form of endocytosis. The semilogarithmic linear size-activity correlation suggests that size-restricted pinocytosis (<100 nm) is effective only for monomeric viruses. The activities of oligomeric and otherwise poorly active beta-Gal-functionalized viruses toward hepatic HepG2 cells are approximately 10(2)-times higher than expected on the size basis, owing to the receptor-mediated specific pathway involving the asialoglycoprotein receptors on the hepatic cell surfaces. The scope and prospect of artificial glycoviruses are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calixarenes*
  • Cytomegalovirus / chemistry*
  • Cytomegalovirus / genetics
  • Genetic Vectors / chemistry*
  • HeLa Cells
  • Humans
  • Luciferases / genetics
  • Particle Size
  • Phenols / chemistry
  • Plasmids / administration & dosage
  • Plasmids / chemistry
  • Polysaccharides / chemistry*
  • Promoter Regions, Genetic
  • Transfection / methods

Substances

  • Phenols
  • Polysaccharides
  • calix(4)arene
  • Calixarenes
  • Luciferases