We propose an interdisciplinary partnership between departments within the Rice University, the Baylor College of Medicine and the University of Texas M.D. Anderson Cancer Center for accelerating the translation of next-generation multimodal nanoparticle-based theranostics. The Consortium's overarching goal is to accelerate the preclinical testing of multifunctional hybrid nanoparticles (hNPs) as multimodal molecular imaging agents and targeted therapeutic agents for the diagnosis and treatment of pancreatic cancer. Specifically this proposal will address the pre-clinical deployment aspects of gold nanostructures with NIR tunable Plasmon resonance. Over the course of this five-year project, a panel of magneto-fluorescent hybrid nanoparticles in the size regimes ranging from 50 to 150 nm will be synthesized for active and passive tumor targeting. In addition to the plasmonics based photo-thermal therapy, we will introduce simultaneous and dramatic enhancement of NIR fluorescence of FDA cleared organic contrast agents within the same nanosystem, thus enabling high throughput and whole body small animal molecular theranostic studies of pancreatic cancer biomarkers with inexpensive NIR optical techniques. Complete vertical integration of all aspects of nano-medicine based cancer intervention research ranging from in vitro validation, mouse models, and to image guided therapy delivery will be achieved via the common quad mode hybrid gold-iron oxide nanostructures. The theranostic modes deployed will shift seamlessly according to the physics of intervention environment by exploiting the complimentary and interdisciplinary expertise of investigators. This consortium will serve as central repository of hNPs that are extensively characterized for physicochemical properties, in vitro and in vivo toxicity, and organ-/tissue-/cellular-biodistribution and pharmacokinetics in multiple animal models. Furthermore, the Consortium will develop rigorous methodologies for plotting the geographic distribution of hNPs within tumors in a quantifiable fashion to facilitate modeling of optically induced thermal damage, a prerequisite for treatment simulation, confomrial dosimetric planning, and treatment delivery upon clinical deployment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA151886-04
Application #
8548283
Study Section
Special Emphasis Panel (ZCA1-SRLB-X (M1))
Program Officer
Morris, Stephanie A
Project Start
2010-09-22
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$267,620
Indirect Cost
$28,941
Name
Rice University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
Lee, Jihyoun; Chatterjee, Dev Kumar; Lee, Min Hyuk et al. (2014) Gold nanoparticles in breast cancer treatment: promise and potential pitfalls. Cancer Lett 347:46-53
Goodman, Amanda M; Cao, Yang; Urban, Cordula et al. (2014) The surprising in vivo instability of near-IR-absorbing hollow Au-Ag nanoshells. ACS Nano 8:3222-31
Ayala-Orozco, Ciceron; Urban, Cordula; Bishnoi, Sandra et al. (2014) Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors. J Control Release 191:90-7
Ayala-Orozco, Ciceron; Urban, Cordula; Knight, Mark W et al. (2014) Au nanomatryoshkas as efficient near-infrared photothermal transducers for cancer treatment: benchmarking against nanoshells. ACS Nano 8:6372-81
Ayala-Orozco, Ciceron; Liu, Jun G; Knight, Mark W et al. (2014) Fluorescence enhancement of molecules inside a gold nanomatryoshka. Nano Lett 14:2926-33
Chen, Wenxue; Ayala-Orozco, Ciceron; Biswal, Nrusingh C et al. (2014) Targeting pancreatic cancer with magneto-fluorescent theranostic gold nanoshells. Nanomedicine (Lond) 9:1209-22
Fang, Zheyu; Zhen, Yu-Rong; Neumann, Oara et al. (2013) Evolution of light-induced vapor generation at a liquid-immersed metallic nanoparticle. Nano Lett 13:1736-42
Bardhan, Rizia; Lal, Surbhi; Joshi, Amit et al. (2011) Theranostic nanoshells: from probe design to imaging and treatment of cancer. Acc Chem Res 44:936-46
Huschka, Ryan; Zuloaga, Jorge; Knight, Mark W et al. (2011) Light-induced release of DNA from gold nanoparticles: nanoshells and nanorods. J Am Chem Soc 133:12247-55