Enhanced-biorecognition and internalization of HPMA copolymers containing multiple or multivalent carbohydrate side-chains by human hepatocarcinoma cells

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing pendant sacc haride moieties (galactosamine, lactose, and triantennary galactose) were s ynthesized. The relationship between the content of saccharide moieties. an d three-dimensional arrangement of galactose residues and their biorecognit ion and internalization by human hepatocarcinoma HepG(2) cells was investig ated. The results obtained clearly indicated preferential binding of the tr ivalent galactose and the lactose-containing copolymers to these cells. The higher the saccharide moieties content in HPMA copolymers, the higher the levels of binding. The biorecognition of the glycosylated HPMA copolymers b y HepG2, cells was inhibited by free lactose. The data on the internalizati on and subcellular trafficking of HPMA copolymer conjugates obtained by con focal fluorescence microscopy correlated well with the flow cytometric anal ysis of their biorecognition by target cells. Structural features of the gl ycosides responsible for the specific recognition of the HPMA copolymers ha ve been identified. The results underline the potential of glycosylated HPM A copolymers for delivery of pharmaceutical agents to hepatocarcinoma cells .