Evaluation of antitumor activities of hyaluronate binding antitumor drugs: synthesis, characterization and antitumor activity
- 1 January 1996
- journal article
- research article
- Published by Informa UK Limited in Journal of Drug Targeting
- Vol. 4 (1), 1-8
- https://doi.org/10.3109/10611869609046255
Abstract
To enhance the selective delivery of antitumor drugs into regional lymph nodes and cancerous tissues via a hyaluronate (HA) receptor (CD44), we synthesized HA-mitomycin C complex and HA-epirubicin complex. To investigate the specific distribution of HA into regional lymph nodes and to evaluate the HA receptor on lewis lung carcinoma cells, we also synthesized 14C-labelled HA and fluorescent HA (FR-HA). The metabolic studies of 14C-HA and HA-epirubicin complex were performed in rats. The specific distribution of both compounds to the lymph nodes were observed after sc treatment. Internalization mechanisms of HA into carcinoma cells (lewis lung carcinoma) via HA receptor was investigated using fluorescent HA (FR-HA) in vitro. Internalization of FR-HA following binding to the cell surfaces was observed. HA-Mitomycin C (MMC) exhibited potent anti-metastatic effects against lewis lung carcinoma implanted in mice at an extremely low dose (0.01 mg/kg) whereas free MMC had no effects.Keywords
This publication has 12 references indexed in Scilit:
- A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps.The Journal of cell biology, 1993
- Significance of CD44 gene products for cancer diagnosis and disease evaluationThe Lancet, 1992
- The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan.The Journal of cell biology, 1992
- A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cellsCell, 1991
- Synthesis and antitumor activity of conjugates of poly(α-malic acid) and 5-fluorouracils bound via ester, amide or carbamoyl bondsJournal of Controlled Release, 1990
- Uptake and degradation of hyaluronan in lymphatic tissueBiochemical Journal, 1988
- Anthracycline antibiotics supported on water-soluble polysaccharides: synthesis and physicochemical characterizationInternational Journal of Biological Macromolecules, 1988
- The cell surface hyaluronate binding sites of invasive human bladder carcinoma cellsBiochemical and Biophysical Research Communications, 1987
- A modified uronic acid carbazole reactionAnalytical Biochemistry, 1962
- Fractionation of hyaluronic acid the polydispersity of hyaluronic acid from the bovine vitreous bodyBiochimica et Biophysica Acta, 1960