Design and development of polymer conjugates as anti-angiogenic agents

Abstract

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is one of the central key steps in tumor progression and metastasis. Consequently, it became an important target in cancer therapy, making novel angiogenesis inhibitors a new modality of anticancer agents. Although relative to conventional chemotherapy, anti-angiogenic agents display a safer toxicity profile, the vast majority of these agents are low-molecular-weight compounds exhibiting poor pharmacokinetic profile with short half-life in the bloodstream and high overall clearance rate. The "Polymer Therapeutics" field has significantly improved the therapeutic potential of low-molecular-weight drugs and proteins for cancer treatment. Drugs can be conjugated to polymeric carriers that can be either directly conjugated to targeting proteins or peptides or derivatized with adapters conjugated to a targeting moiety. This approach holds a significant promise for the development of new targeted anti-angiogenic therapies as well as for the optimization of existing anti-angiogenic drugs or polypeptides. Here we overview the innovative approach of targeting tumor angiogenesis using polymer therapeutics.