Polymerizable Fab' antibody fragments for targeting of anticancer
drugs
Zheng-Rong Lu, Pavla Kopeková
& Jindich Kopeek
Departments of Pharmaceutics and Pharmaceutical Chemistry/CCCD,
and of Bioengineering, University of Utah, Salt Lake City,
UT 84112.
Correspondence should be addressed to Jindich Kopeek Jindrich.Kopecek@m.cc.utah.eduPolymerizable Fab'HPMA copolymerdrug targetingchlorin e6anticancer drug
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.