Targetable Polymer - Antiangiogenic Drug Conjugates for Systemic Breast Cancer Therapy

摘要

The overall purpose of this project is to develop targetable water- soluble polymerantiangiogenic drug conjugates for systemic breast cancer therapy. The rationale is that by selectively targeting polymer-antiangiogenic drug conjugates to alpha-v-beta-3 receptors on endothelial cells of tumor neovasculature; it is possible to restrict the biodistribution of the antiangiogenic drug to the vascular space, thereby increasing tumor accumulation and subsequent antitumor potency of the drug and decreasing dose- limiting toxicity. In year 1 progress was made in the following areas: (i) Synthesis of a series targetable HPMA copolymerantiangiogenic drug conjugates, (ii) Physicochemical characterization of the synthesized conjugates. There were challenges in the synthetic strategy for derivatization of the drug to attach to the polymer backbone. Current work is under way during the no cost extension period to optimize the synthetic strategies and to complete the remaining Aims of the grant, i.e., determination of binding and antiangiogenic efficacy of the conjugates on model endothelial cell lines.