Synergism of Selective Tumor Vascular Thrombosis and Protease Activated Prodrug
Abstract
Targeted drug activation at selected site promises reduced toxicity and enhanced efficacy. We propose to investigate and validate a bipartite drug delivery-activation system that employs selective tumor vascular targeted induction of endogenous coagulation protease cascade followed by administration of protease-activated prodrug. The activation of coagulation cascade and tumor vascular thrombosis as well as the following activation of the thrombolytic pathways led to explosive amplification of serine protease cascades and local proteolytic activity within the tumor vasculature. This tumor specific proteolytic activity is exploited for targeted local prodrug activation. The combination treatment of selective tumor vascular thrombosis and protease-activated prodrug demonstrated profound synergism. This coordinated attack on tumors resulted in complete tumor eradication in multiple drug resistant rodent and human tumor models with no apparent toxicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2008
- Accession Number
- ADA494207
Entities
People
- Fengwei Liu
Organizations
- Scripps Research