Synthesis and biological evaluation of paclitaxel-C225 conjugate as a model for targeted drug delivery.

摘要: Tumor-targeted drug delivery is an attractive strategy in cancer treatment. We have previously reported a paclitaxel model conjugate using bombesin receptor-recognizing peptide which the cytotoxicity against H1299 human nonsmall cell lung was enhanced compared to unconjugated taxol. In effort expand development of tumor-recognizing taxanes, (PTX, taxol) conjugated anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MAb) Erbitux (C225) serve as MAb-mediated compound. Thus, derivatized at its 2‘-hydroxy function by introduction succinate linker, and carboxyl group latter covalently attached C225 through amide bond formation. The final product (PTXC225) analyzed mass spectrometrically for assessment drug-to-antibody ratios. Cytotoxicity screening drug-antibody A431, UM-SCC-1, UM-SCC-6 cells indicated enhancement cytocidal ef...