A NOVEL THERANOSTIC PLATFORM FOR TARGETED CANCER THERAPY AND TREATMENT MONITORING


Year of Award:
2013
Award Type:
R21
Project Number:
CA174541
RFA Number:
RFA-CA-12-002
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
BAI, MINGFENG
Other PI or Project Leader:
N/A
Institution:
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Cancer treatment currently relies heavily upon administration of cytotoxic drugs that attack both cancerous and healthy cells due to limited selectivity of drugs. Therapeutic efficacy and systemic toxicity can be improved by employing a multifunctional drug delivery system that allows targeted drug delivery, controlled drug release and therapeutic effect monitoring. The integration of therapeutic and diagnostic treatments has created a new genre in patient care and personalized medicine termed theranostics. Dendrimers provide an ideal theranostic platform due to their precisely controlled size, shape, and surface chemistry. These unique properties allow dendrimers to be developed with high structural monodispersity, desired plasma circulation time and biodistribution properties, as well as control over drug release. In our pioneering approach, we aim to develop the first quaterrylene-based (QR) near-infrared (NIR) fluorescent theranostic dendrimer platform and seek to shift NIR theranostic dendrimers away from those with poor chemical stability, quantum yield and photostability to a highly chemically stable, fluorescent and photostable NIR theranostic platform. As a proof-of-principle study to demonstrate that the QR theranostic dendrimers can be applied in targeted cancer imaging, we will attach a conjugable translocator protein (TSPO) ligand to the selected dendrimers and image the targeted agents in TSPO over-expressing breast cancer cells and in an animal model. We hypothesize that a quaterrylene-based dendrimer will provide a highly photostable, fluorescent and chemically stable theranostic platform for targeted cancer therapy and efficacy monitoring. Such innovative design avoids the photobleaching and self-quenching issues of current technology, thus allowing NIR theranostic studies with longer imaging time, higher fluorescence signal and more accurate quantification. It will be possible to conjugate various targeting molecules, signaling moieties and drugs to this innovative platform and therefore, this platform has the potential to be widely applied in cancer treatment and may transform the way that cancer patients are treated and monitored.