Targetable Polymer-Antiangiogenic Drug Conjugates for Systemic Breast Cancer Therapy
Abstract
The overall purpose of this project is to develop targetable water-soluble polymer-antiangiogenic 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 the following were accomplished: i) Synthesis of a series of targetable HPMA copolymerantiangiogenic drug conjugates; ii) Physicochemical characterization of the synthesized conjugates. In year 2 (no cost extension period the following wasaccomplished: iii) In vitro evaluation of targeting efficacy of the synthesized conjugates against model endothelial cell line and iv) In vitro evaluation of antiproliferative efficacy of the synthesized conjugates against the same cell line. Additionally synthetic strategies were established to modify the drug with a lysosomally degradable spacer. Results demonstrate the feasibility of synthesizing angiogenesis targetable HPMA copolymer drug conjugates and their potential in specifically binding to endothelial cell surface receptors as well as causing inhibition of cell proliferation. Overall these conjugates have the potential to treat breast cancer by inhibiting the angiogenic vasculature around the tumor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA462903
Entities
People
- Anjan Nan
Organizations
- University of Maryland, Baltimore