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Conjugates of Antibody‐Targeted PEG Multiblock Polymers with Doxorubicin in Cancer Therapy
Author(s) -
Pechar Michal,
Ulbrich Karel,
Jelínková Markéta,
Říhová Blanka
Publication year - 2003
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.200350004
Subject(s) - chemistry , conjugate , peg ratio , doxorubicin , ethylene glycol , drug carrier , concanavalin a , in vivo , combinatorial chemistry , biochemistry , in vitro , organic chemistry , drug delivery , biology , mathematical analysis , mathematics , microbiology and biotechnology , finance , chemotherapy , economics , genetics
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.