Remarkably size-regulated cell invasion by artificial viruses. Saccharide-dependent self-aggregation of glycoviruses and its consequences in glycoviral gene delivery.
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.
Nakai
Takashi
T
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Kanamori
Takuya
T
Sando
Shinsuke
S
Aoyama
Yasuhiro
Y
D047250:Calixarenes; D003587:Cytomegalovirus / Q000737:chemistry* / Q000235:genetics; D005822:Genetic Vectors / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010316:Particle Size; D010636:Phenols / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D014162:Transfection / Q000379:methods
D010636:Phenols; D011134:Polysaccharides; C121325:calix(4)arene; D047250:Calixarenes; D008156:Luciferases