Synthesis and selective cytotoxicity of a hyaluronic acid-antitumor bioconjugate

A cell-targeted prodrug was developed for the anti-cancer drug Taxol, using hyaluronic acid (HA) as the drug carrier. HA-Taxol bioconjugates were synt hesized by linking the Taxol 2'-OH via a succinate ester to adipic dihydraz ide-modified HA (HA-ADH). The coupling of Taxol-NHS ester and HA-ADH provid ed several HA bioconjugates with different levels of ADH modification and d ifferent Taxol loadings. A fluorescent BODIPY-HA was also synthesized to il lustrate cell targeting and uptake of chemically modified HA using confocal microscopy. HA-Taxol conjugates showed selective toxicity toward the human cancer cell lines (breast, colon, and ovarian) that are known to overexpre ss HA. receptors, while no toxicity was observed toward a mouse fibroblast cell line at the same concentrations used with the cancer cells. The drug c arrier HA-ADH was completely nontoxic. The selective cytotoxicity is consis tent with the results from confocal microscopy, which demonstrated that BOD IPY-HA only entered the cancer cell lines.