Biorecognition of HPMA copolymer-lectin conjugates as an indicator of differentiation of cell-surface glycoproteins in development, maturation, and diseases of human and rodent gastrointestinal tissues
S. Wroblewski et al., Biorecognition of HPMA copolymer-lectin conjugates as an indicator of differentiation of cell-surface glycoproteins in development, maturation, and diseases of human and rodent gastrointestinal tissues, J BIOMED MR, 51(3), 2000, pp. 329-342
Lectins are proteins that bind glycoproteins; binding patterns are altered
with changes in glycoprotein expression accompanying maturation or disease.
Binding of two lectins, wheat germ agglutinin (WGA) and peanut agglutinin
(PNA), in human and rodent colon were previously examined. Normal tissue sh
owed intense WGA binding; PNA binding was minimal. Diseased tissues showed
increased PNA binding. We hypothesized that N-(2-hydroxypropyl)methacrylami
de (HPMA) copolymer-lectin-drug conjugates could deliver therapeutic agents
to diseased tissues by targeting colonic glycoproteins. We examined biorec
ognition of free and HPMA copolymer-conjugated WGA and PNA and anti-Thomsen
-Friedenreich (TF) antigen antibody binding in normal neonatal, adult, and
diseased rodent tissues, human specimens of inflammation, and Barrett's eso
phagus. Neonatal WGA binding was comparable to the adult, with additional l
uminal columnar cell binding. PNA binding was more prevalent; luminal colum
nar cell binding existed during the first 2.5 weeks of Life. WGA binding wa
s strong in both normal and diseased adult tissues; a slight decrease was n
oted in disease. PNA binding was minimal in normal tissues; increases were
seen in disease. Anti-TF antigen antibody studies showed that PNA did not b
ind to the antigen. The results suggest that HPMA copolymer-lectin-drug con
jugates may provide site-specific treatment of conditions such as colitis a
nd Barrett's esophagus. (C) 2000 John Wiley & Sons, Inc.