Polymerizable Fab' antibody fragments for targeting of anticancer drugs

Nat Biotechnol. 1999 Nov;17(11):1101-4. doi: 10.1038/15085.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Carcinoma / drug therapy
  • Drug Carriers
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / administration & dosage
  • Immunoglobulin Fab Fragments / chemistry*
  • Methacrylates / chemistry
  • Ovarian Neoplasms / drug therapy
  • Polymers / administration & dosage
  • Polymers / chemistry*
  • Porphyrins / chemistry
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Immunoglobulin Fab Fragments
  • Methacrylates
  • Polymers
  • Porphyrins
  • hydroxypropyl methacrylate