Polymeric drugs based on conjugates of synthetic and natural macromolecules. I. Synthesis and physico-chemical characterisation.
This paper describes the synthesis, physico-chemical characteristics and results of selected biological tests of conjugates of antibodies or proteins with poly(HPMA) or with poly(HPMA) carriers of anti-cancer drug doxorubicin, designed for targeted cancer therapy. Two types of conjugates differing in the method of conjugation of polymer with protein were synthesized. In the first, protein is attached to the polymer via an oligopeptide sequence in the side chain of the polymer backbone and, in the second, the polymer is attached to protein via its end-chain functional group. Conjugation of an antibody with poly(HPMA) does not influence the binding activity of the antibody for cell surface antigen. The physico-chemical characteristics and biological activity of both systems depend on the detailed structure of the polymer, the type of antibody or protein moiety and the structure of the whole system.
Ulbrich
K
K
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06, Prague, Czech Republic. office@imc.cas.cz
Subr
V
V
Strohalm
J
J
Plocová
D
D
Jelínková
M
M
Ríhová
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001665:Binding Sites; D004317:Doxorubicin / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D066298:In Vitro Techniques; D008223:Lymphoma / Q000188:drug therapy*; D046911:Macromolecular Substances; D008297:Male; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D004337:Drug Carriers; D046911:Macromolecular Substances; D008689:Methacrylates; D009842:Oligopeptides; D011108:Polymers; D011506:Proteins; D004317:Doxorubicin; C032802:hydroxypropyl methacrylate