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

被引:65
作者
David, A
Kopecková, P
Rubinstein, A
Kopecek, J
机构
[1] Hebrew Univ Jerusalem, Sch Pharm, Fac Med, IL-91120 Jerusalem, Israel
[2] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA
关键词
D O I
10.1021/bc010026v
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing pendant saccharide moieties (galactosamine, lactose, and triantennary galactose) were synthesized. The relationship between the content of saccharide moieties. and three-dimensional arrangement of galactose residues and their biorecognition and internalization by human hepatocarcinoma HepG(2) cells was investigated. The results obtained clearly indicated preferential binding of the trivalent 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 by HepG2, cells was inhibited by free lactose. The data on the internalization and subcellular trafficking of HPMA copolymer conjugates obtained by confocal fluorescence microscopy correlated well with the flow cytometric analysis of their biorecognition by target cells. Structural features of the glycosides responsible for the specific recognition of the HPMA copolymers have been identified. The results underline the potential of glycosylated HPMA copolymers for delivery of pharmaceutical agents to hepatocarcinoma cells.
引用
收藏
页码:890 / 899
页数:10
相关论文
共 55 条
[1]   CARBOHYDRATE-SPECIFIC RECEPTORS OF THE LIVER [J].
ASHWELL, G ;
HARFORD, J .
ANNUAL REVIEW OF BIOCHEMISTRY, 1982, 51 :531-554
[2]  
Chaplin M.F., 1986, CARBOHYDRATE ANAL PR, P2
[3]   Carbohydrate recognition systems: Functional triads in cell-cell interactions [J].
Crocker, PR ;
Feizi, T .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 1996, 6 (05) :679-691
[4]   MURAMYL DIPEPTIDE BOUND TO POLY-L-LYSINE SUBSTITUTED WITH MANNOSE AND GLUCONOYL RESIDUES AS MACROPHAGE ACTIVATORS [J].
DERRIEN, D ;
MIDOUX, P ;
PETIT, C ;
NEGRE, E ;
MAYER, R ;
MONSIGNY, M ;
ROCHE, AC .
GLYCOCONJUGATE JOURNAL, 1989, 6 (02) :241-255
[5]   CA2+-DEPENDENT CARBOHYDRATE-RECOGNITION DOMAINS IN ANIMAL PROTEINS [J].
DRICKAMER, K .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 1993, 3 (03) :393-400
[6]   ANTICANCER AGENTS COUPLED TO N-(2-HYDROXYPROPYL)METHACRYLAMIDE COPOLYMERS .3. EVALUATION OF ADRIAMYCIN CONJUGATES AGAINST MOUSE LEUKEMIA-L1210 INVIVO [J].
DUNCAN, R ;
HUME, IC ;
KOPECKOVA, P ;
ULBRICH, K ;
STROHALM, J ;
KOPECEK, J .
JOURNAL OF CONTROLLED RELEASE, 1989, 10 (01) :51-63
[7]   FATE OF N-(2-HYDROXYPROPYL)METHACRYLAMIDE COPOLYMERS WITH PENDENT GALACTOSAMINE RESIDUES AFTER INTRAVENOUS ADMINISTRATION TO RATS [J].
DUNCAN, R ;
SEYMOUR, LCW ;
SCARLETT, L ;
LLOYD, JB ;
REJMANOVA, P ;
KOPECEK, J .
BIOCHIMICA ET BIOPHYSICA ACTA, 1986, 880 (01) :62-71
[8]   TARGETING OF N-(2-HYDROXYPROPYL)METHACRYLAMIDE CO-POLYMERS TO LIVER BY INCORPORATION OF GALACTOSE RESIDUES [J].
DUNCAN, R ;
KOPECEK, J ;
REJMANOVA, P ;
LLOYD, JB .
BIOCHIMICA ET BIOPHYSICA ACTA, 1983, 755 (03) :518-521
[9]   GALACTOSYLATED POLY(L-LYSINE) AS A HEPATOTROPIC CARRIER OF 9-BETA-D-ARABINOFURANOSYLADENINE 5'-MONOPHOSPHATE [J].
FIUME, L ;
BASSI, B ;
BUSI, C ;
MATTIOLI, A ;
SPINOSA, G ;
FAULSTICH, H .
FEBS LETTERS, 1986, 203 (02) :203-206
[10]  
HUDGIN RL, 1974, J BIOL CHEM, V249, P7369