Nanotechnology has the potential to significantly impact the development of small animal models of cancer? including models to test new antineoplastic therapies. In this project we will develop mouse tumor xenoqraft? models that will allow us to test if we can combine both tissue/serum nanosensor based proteomic analysis? and molecular imaging with targeted fluorescent quantum dots to predict and monitor treatment response? with specific therapies. These models are important to the overall vision of this CCNE-TR for which would? like to eventually utilize ex vivo nanosensors and in vivo molecular imaging in cancer patients for improving? how we predict and monitor response to therapies.
In Aim 1 we will optimize small animal optical imaging? instrumentation for imaging quantum dots and also work with General Electric Global Research to develop? and test a new frequency domain optical imaging instrument.
In Aim 2 we will utilize biologically targeted? quantum dots developed in Projects 5 and 6 to image tumors in living mice. We will proceed systematically? from targeting one known tumor cell surface antigen (CD20 in our lymphoma xenograft model) to targeting? several known tumor cell surface antigens (her2/her3/PSCA in our prostate cancer model), before expanding? our target range to neovascularization (avp3 Integrin) and extracellular matrix targets (Matrix? metalloproteinase 2, MMP2).
In Aim 3 we will develop mouse models of lymphoma for testing antineoplastic? therapies in order to study changes in proteins at the cell membrane, in the secretome, and in serum. Cell? surface and serum proteome will be analyzed by Solid Phase Extraction of Glycoproteins (SPEC) and Liquid? Chromatography Mass Spectrometry (SPEG/MS), whereas secretome will be assessed by biotin capture? and subsequent cellular functional profiling array for changes that are predictive of response to therapy. We? will test two lymphoma therapy models, one xenograft model for human lymphoma mimicking response vs.? resistance to Rituxan therapy, and a mouse pre-clinical model of response vs. resistance to targeted? inactivation of the MYC oncogene.
In Aim 4 we will test a mouse cancer model using the results from the? previous three aims in order to determine the utility of integrating ex vivo and in vivo nanotechnologies to? determine protein changes in the tissue/serum and to image molecular changes pre and post-therapy. The? significance of this work is that it should help set the foundation for using ex vivo nanosensors in clinical? trials, to allow development of novel molecular imaging probes for clinical trials, and to improve drug testing? in small animal cancer models. This should lead to marked improvement in predicting and monitoring? response to therapy in cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA119367-02
Application #
7485826
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
2
Fiscal Year
2007
Total Cost
$622,465
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Shah, Preyas N; Lin, Tiras Y; Aanei, Ioana L et al. (2018) Extravasation of Brownian Spheroidal Nanoparticles through Vascular Pores. Biophys J 115:1103-1115
Shou, Kangquan; Qu, Chunrong; Sun, Yao et al. (2017) Multifunctional biomedical imaging in physiological and pathological conditions using a NIR-II probe. Adv Funct Mater 27:
Feng, Yi; Zhu, Shoujun; Antaris, Alexander L et al. (2017) Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore. Chem Sci 8:3703-3711
Willmann, J├╝rgen K; Bonomo, Lorenzo; Carla Testa, Antonia et al. (2017) Ultrasound Molecular Imaging With BR55 in Patients With Breast and Ovarian Lesions: First-in-Human Results. J Clin Oncol 35:2133-2140
Kani, Kian; Garri, Carolina; Tiemann, Katrin et al. (2017) JUN-Mediated Downregulation of EGFR Signaling Is Associated with Resistance to Gefitinib in EGFR-mutant NSCLC Cell Lines. Mol Cancer Ther 16:1645-1657
Antaris, Alexander L; Chen, Hao; Diao, Shuo et al. (2017) A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. Nat Commun 8:15269
Smith, Bryan Ronain; Gambhir, Sanjiv Sam (2017) Nanomaterials for In Vivo Imaging. Chem Rev 117:901-986
Antaris, Alexander L; Chen, Hao; Cheng, Kai et al. (2016) A small-molecule dye for NIR-II imaging. Nat Mater 15:235-42
Pu, Kanyi; Chattopadhyay, Niladri; Rao, Jianghong (2016) Recent advances of semiconducting polymer nanoparticles in in vivo molecular imaging. J Control Release 240:312-322
Zhang, Ruiping; Cheng, Kai; Antaris, Alexander L et al. (2016) Hybrid anisotropic nanostructures for dual-modal cancer imaging and image-guided chemo-thermo therapies. Biomaterials 103:265-277

Showing the most recent 10 out of 228 publications