ORGN 70 |
| A covalently crosslinked synthetic extracellular matrix (sECM) was developed for 3-D culture of cells in vitro and in vivo. Chemically-modified hyaluronan (HA), other glycosaminoglycans (GAGs), and ECM polypeptides containing thiol residues are crosslinked using biocompatible polyvalent electrophiles. We describe two applications of the sECM technology for evaluation of drug efficacy and drug toxicity: (i) drug hepatotoxicity and (ii) anticancer drug efficacy. First, primary hepatocytes retain their biochemical phenotypes and achieve greater longevity in 3-D culture in the sECM, providing rapid evaluation of hepatotoxicity in vitro. Implantation of human liver cell-seeded sECMs into nude mice gives an in vivo model. Second, orthotopic injection of tumor cells (either cell line or patient-derived) in an in situ-crosslinked sECM hydrogel in nude mice gives a new xenograft model and offers a superior protocol for metastatic cancer. We employed “tumor engineering” to evaluate signal transduction modifiers and conventional chemotherapeutic drugs for breast, colon, and pancreatic cancer. |
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New Molecular Strategies for Tumor-Targeting Drug Delivery
1:25 PM-5:20 PM, Sunday, August 19, 2007 BCEC -- 253 A/B/C, Oral
Division of Organic Chemistry |