Polymerizable Fab' antibody fragments for targeting of anticancer drugs.
We have designed a new pathway for the synthesis of targeted polymeric drug delivery systems, using polymerizable antibody Fab' fragments (MA-Fab'). The targeted systems can be directly prepared by copolymerization of the MA-Fab', N-(2-hydroxypropyl)methacrylamide (HPMA) and drug-containing monomers. Both MA-Fab' and the Fab'-targeted copolymers can effectively bind to target cells. An MA-Fab' (from OV-TL 16 Ab) targeted HPMA copolymer containing mesochlorin e6 (Mce6) was synthesized by copolymerization of MA-Fab', HPMA, and MA-GFLG-Mce6. The targeted copolymer exhibited a higher cytotoxicity toward OVCAR-3 human ovarian carcinoma cells than the nontargeted Mce6-containing copolymer or free Mce6. The targeted copolymer was internalized more efficiently by OVCAR-3 cells than the nontargeted copolymer.
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Z R
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Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, UT 84112, USA.
Kopecková
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P
Kopecek
J
J
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002277:Carcinoma / Q000188:drug therapy; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D008689:Methacrylates; D011108:Polymers; D011166:Porphyrins; C032802:hydroxypropyl methacrylate