Although anti-angiogenic agents offer great therapeutic potential, preclinical and clinical studies suggest that these agents, used as monotherapies, have a delayed onset of activity and may have only limited effects on advanced malignancies. Multimodality targeted polymer therapeutics that include anti-angiogenic agents and chemotherapeutics offer the potential for improved efficacy and diminished toxicity in the treatment of cancer and other angiogenesis-dependent diseases. We have recently designed and characterized novel combined anti-angiogenic and antitumor polymerdrug conjugates that target both the tumor and its microenvironment. These conjugates include combined anti-angiogenic and chemotherapeutic drugs, such as TNP-470 and paclitaxel, respectively. Several conjugates also incorporate bisphosphonates as targeting moieties for bone metastases and osteosarcomas or RGD peptidomimetics that target integrins overexpressed on tumor endothelial cells and several tumor cells. Using molecular imaging techniques, we have successfully established dormant and fast-growing tumor mouse models to intravitally non-invasively follow-up tumor progression and response to novel polymer therapeutics. Our results point at our polymer therapeutics as novel bi-specific conjugates targeting both the tumor epithelial and endothelial compartments, warranting their use on a wide spectrum of primary as well as metastatic tumors. The use of these novel architectures will potentially shed light on the molecular mechanisms underlying tumor dormancy and hopefully transform cancer into a chronically-manageable disease.
- Polymer therapeutics
- Targeted drug delivery