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Synthesis and Cytotoxic Activity of Macromolecular Prodrug of Cisplatin Using Poly(ethylene glycol) with Galactose Residues or Antennary Galactose Units
Author(s) -
Ohya Yuichi,
Nagatomi Kazuya,
Ouchi Tatsuro
Publication year - 2001
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 - 10.1002/1616-5195(20011101)1:8<355::aid-mabi355>3.0.co;2-q
Subject(s) - chemistry , conjugate , prodrug , peg ratio , ethylene glycol , galactose , cisplatin , in vitro , biochemistry , stereochemistry , biology , organic chemistry , mathematical analysis , mathematics , finance , chemotherapy , economics , genetics
To provide a macromolecular prodrug with recognition ability for hepatoma cells, we synthesized new conjugates of cisplatin (CDDP) and poly(ethylene glycol) (PEG) with galactose residues or antennary galactose units (Gal4A, four branched galactose residues) at the chain terminus, Gal‐PEG‐DA/CDDP or Gal4A‐PEG‐DA/CDDP conjugates. An antennary (branched) structure of Gal4A was designed based on the fact that saccharide clusters with branched structures show highly effective binding with saccharide receptors, a phenomenon known as the ‘cluster effect’. The cytotoxic activity of the conjugates was investigated against HepG2 human hepatoma cells in vitro and compared with a control conjugate without galactose, MeO‐PEG‐DA/CDDP. Gal‐PEG‐DA/CDDP and Gal4A‐PEG‐DA/CDDP conjugates showed lower IC 50 values (3.1×10 –4 and 2.3×10 –4 M , respectively) than the MeO‐PEG‐DA/CDDP conjugate (10.5×10 –4 M ). The cytotoxic activities of these conjugates with galactose residues or antennary galactose units were inhibited as a result of the addition of galactose and strongly inhibited by the addition of Gal4A, however the inclusion of a methoxy group (the MeO‐PEG‐DA/CDDP conjugate) did not affect the activity. These results suggest that the Gal4A unit introduced to the conjugate has effective recognition ability against HepG2 human hepatoma cells.