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.

Public Health Relevance

The primary goal of this application is to develop an innovative near-infrared (NIR) theranostic (therapeutic + diagnostic) dendrimer platform for targeted cancer therapy and therapeutic monitoring. This unique theranostic platform will allow longer imaging time, higher fluorescence signal and more accurate quantification, thereby creating the potential for personalized medicine and transforming the way that cancer patients are treated and monitored.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA174541-02
Application #
8658416
Study Section
Special Emphasis Panel (ZCA1-SRLB-Q (J1))
Program Officer
Mazurchuk, Richard V
Project Start
2013-05-03
Project End
2016-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
$227,063
Indirect Cost
$79,380
Name
University of Pittsburgh
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Janjic, Jelena M; Shao, Pin; Zhang, Shaojuan et al. (2014) Perfluorocarbon nanoemulsions with fluorescent, colloidal and magnetic properties. Biomaterials 35:4958-68
Shao, Pin; Jia, Ningyang; Zhang, Shaojuan et al. (2014) Synthesis and optical properties of water-soluble biperylene-based dendrimers. Chem Commun (Camb) 50:5648-51