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.
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 showed intense WGA binding; PNA binding was minimal. Diseased tissues showed increased PNA binding. We hypothesized that N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-lectin-drug conjugates could deliver therapeutic agents to diseased tissues by targeting colonic glycoproteins. We examined biorecognition 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 esophagus. Neonatal WGA binding was comparable to the adult, with additional luminal columnar cell binding. PNA binding was more prevalent; luminal columnar cell binding existed during the first 2.5 weeks of life. WGA binding was strong in both normal and diseased adult tissues; a slight decrease was noted in disease. PNA binding was minimal in normal tissues; increases were seen in disease. Anti-TF antigen antibody studies showed that PNA did not bind to the antigen. The results suggest that HPMA copolymer-lectin-drug conjugates may provide site-specific treatment of conditions such as colitis and Barrett's esophagus.
Wróblewski
S
S
Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA.
Berenson
M
M
Kopecková
P
P
Kopecek
J
J
D000818:Animals; D000831:Animals, Newborn; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D001672:Biocompatible Materials; D003092:Colitis / Q000378:metabolism / Q000473:pathology; D004064:Digestive System / Q000254:growth & development / Q000378:metabolism*; D005767:Gastrointestinal Diseases / Q000378:metabolism* / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology; D037102:Lectins; D008297:Male; D008422:Materials Testing; D008565:Membrane Proteins / Q000378:metabolism; D008689:Methacrylates; D019887:Peanut Agglutinin / Q000378:metabolism; D011108:Polymers; D051381:Rats; D011916:Rats, Inbred F344; D014909:Wheat Germ Agglutinins / Q000378:metabolism
D001672:Biocompatible Materials; D006023:Glycoproteins; D037102:Lectins; D008565:Membrane Proteins; D008689:Methacrylates; D019887:Peanut Agglutinin; D011108:Polymers; D014909:Wheat Germ Agglutinins; C032802:hydroxypropyl methacrylate