Conjugates of Antibody-Targeted PEG Multiblock Polymers with Doxorubicin in Cancer Therapy
✍ Scribed by Michal Pechar; Karel Ulbrich; Markéta Jelínková; Blanka Říhová
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 213 KB
- Volume
- 3
- Category
- Article
- ISSN
- 1616-5187
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✦ Synopsis
Abstract
The synthesis and physico‐chemical characterisation of biodegradable multiblock polymer drug carriers based on poly(ethylene glycol) (PEG) are described. The blocks of PEG (${{\bar{M}}_{\rm w}}$ = 2 000) are interconnected by an enzymatically degradable tripeptide derivative consisting of one Lys and two Glu residues. An anticancer drug, doxorubicin (Dox), was attached to the polymer carrier by a Gly‐Phe‐Leu‐Gly tetrapeptide spacer, which is also susceptible to degradation by lysosomal enzymes. A targeting polyclonal antibody was covalently linked to the polymer‐Dox conjugate by the aminolytic reaction of reactive sulfosuccinimidyl ester groups of the polymer with the protein. The resulting antibody‐polymer‐drug conjugates were characterised by SEC, UV/VIS spectrophotometry and amino acid analysis. Although the studied polymers show only a moderate antiproliferative activity against concanavalin A‐stimulated murine splenocytes and a murine T‐cell EL 4 lymphoma in vitro, they exhibited significant antitumour efficiency against murine T‐cell EL 4 lymphoma in vivo.
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