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Polymerizable Fab′ antibody fragments for targeting of anticancer drugs

Nature Biotechnology volume 17, pages 1101–1104 (1999)Cite this article

Abstract

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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Figure 1: (A) Preparation of N-(N-methacryloyl-6-aminocaproyl-6-aminocaproyl), N′-(3-maleimido-propionyl)-1,6-diaminohexane (MMDA).
Figure 2
Figure 3: The viability of OVCAR-3 human carcinoma cells in the presence of poly(HPMA-co-MA-Fab′-co-MA-Mce6) (♦), Mce 6 (▪) and poly(HPMA-co-MA-Mce6) (●).
Figure 4

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Acknowledgements

We thank Dr. L. Poels (University of Nijmegen, The Netherlands) for the generous gift of the hybridoma producing OV-TL 16 antibody, and Dr. Z. Wu for collecting the MALDI-TOF mass spectra of the antibody and its fragments. This research was supported in part by NIH grant CA51578 from the National Cancer Institute, and by the Center for Biopolymers at Interfaces, University of Utah.

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  1. Departments of Pharmaceutics and Pharmaceutical Chemistry/CCCD and of Bioengineering, University of Utah, Salt Lake City, 84112, UT

    Zheng-Rong Lu, Pavla Kopečková & Jindřich Kopeček

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  1. Zheng-Rong Lu
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Correspondence to Jindřich Kopeček.

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Lu, ZR., Kopečková, P. & Kopeček, J. Polymerizable Fab′ antibody fragments for targeting of anticancer drugs. Nat Biotechnol 17, 1101–1104 (1999). https://doi.org/10.1038/15085

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