CCNE Alliance Challenge Projects
Texas Center for Cancer Nanomedicine (TCCN) has participated in the Nanotechnology community by developing the following projects with three CCNEs. These projects were funded based on the guidelines set by NCI. The projects and funding were reviewed and approved by NCI and now extended to ROUND 2 of Alliance Challenge Projects.
Project 1: Metronomic therapy of Ovarian Cancer
Joseph De Simone, Carolina Center of Cancer Nanotechnology Excellence, University of North Carolina; Anil K. Sood, Gabriel Lopez-Berestein, Texas Center for Nanomedicine, MD Anderson Cancer Center
OVERALL GOAL: In a convergent and synergistic CCNE Alliance Challenge proposal, we intend to exploit the nanotechnology breakthroughs of the Texas Center for Cancer Nanomedicine and the Carolina Center of Cancer Nanotechnology Excellence to explore the use of combination of PLGA PRINT (Poly lactic acid-co-glycolic acid Particle Replication in Non-wetting Templates) based Docetaxel (Doc) and Chitosan-EZH2 siRNA to develop metronomic chemotherapy (frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells).
Aim 1: To determine the combined tumor vessel effects of PLGA-Doc and Chitosan EZH2 siRNA in orthotopic animal models;
Aim 2: To determine the antitumor efficacy of the combination PLGA-Doc and Chitosan-EZH2 siRNA in orthotopic models of Ovarian Cancer.
SYNERGY & COLLABORATION: These studies are synergistic as the models and the nanoparticle systems are ONLY available within each investigator’s laboratory.
Project 2: Multiplexed Molecularly Targeted Theranostics of Aberrant Vasculature in Pancreatic Cancer
Amit Joshi, Ph.D. Department of Radiology, Baylor College of Medicine; Naomi Halas, Ph.D. Electrical and Computer Engineering, Rice University; David G. Gorenstein, Ph.D. Institute of Molecular Medicine Department of NanoMedicine and Biomedical Engineering, UT Health Science Center
Abstract: We propose the development and validation of hybrid magneto-fluorescent silica gold nanoparticles (hNP) for multimodal imaging of inflamed vasculature associated with pancreatic cancer. By varying the core/shell sizes of silica core gold nanoparticles, the plasmon resonance can be finely tuned over the NIR region for enabling optical imaging and photothermal therapy at resonant wavelengths. We have demonstrated that by coupling NIR fluorophores with gold nanoshells, the fluorescence yield can be dramatically enhanced, and additional imaging contrasts can be in induced in the same nanostructures via incorporation of MR contrast agents. Via coupling of E-selectin binding thioaptamers to magneto-fluorescent nanoparticles, inflamed vasculature associated with tumors can be selectively targeted for image-guided therapy. As Eselectin is only expressed on endothelial cells in response to inflammatory stimuli and is absent in normal vessels, high affinity and low immunogenic thioaptamers provide an attractive source of ligands for preferential accumulation of hNPs in tumor vasculature and metastatic sites following systemic delivery.
AIMS: (i) develop conjugates of hNPs with TA for targeting E-selectin expression and validate them in vitro in endothelial cells, and in vivo for pancreatic cancer xenografts, (ii) study and optimize the bio-distribution of hNP-TA constructs in nude mice models via time dependent whole body NIR optical and MR imaging and finally (iii) implement multiplexed imaging of pancreatic tumors and associated vasculature by deploying two hNP constructs with different Plasmon wavelengths, with one targeted to Eselectin expression on the vasculature, and the other targeted to NGaL over-expression in the pancreatic cancer cells.
Project 3: Nanoconstruct-Based Dual Imaging of Single Metastatic Cells In Vivo
Paolo Decuzzi, Ph.D. Dept. of Nanomedicine and Biomedical Engineering @ The Methodist Hospital Research Institute (TCCN); Brian Rutt, Ph.D.Department of Radiology @ Stanford School of Medicine (CCNE-T)
Nanoparticles can be loaded with a multitude of different contrast agents (CAs) enabling multimodal imaging and providing signal enhancement. The size, shape and surface properties of nanoparticles can be rationally designed to favor their preferential accumulation at the targeted site, upon systemic administration. Here, we propose the development and preliminary in vitro/invivo characterization of a dual imaging nanoconstruct (NC) for cancer and single cell imaging. FDA approved and commercially available contrast agents for MRI (Gd-DTPA) and SPECT/CT (111In-DTPA) will be co-loaded in the nanoporous structure of rationally-designed silicon nanoparticles. The NC will blend together the high spatial resolution offered by MR imaging, the high sensitivity of nuclear imaging and the highly efficient tumor accumulation recently demonstrated for the rationally-designed silicon particles. The proposed activity will be co-developed by the group of Dr. Decuzzi (Texas Center for Cancer Nanomedicine (TCCN) at TMHRI – Houston), who has a long experience in the rational design of nanoparticles and has recently demonstrated the potential of a Gd-DTPA based nanoconstruct; and the group of Dr. Rutt (Center for Cancer Nanotechnology Excellence and Translation (CCNE-T) at Stanford University), who has a long experience in the application and development of different techniques for single cell imaging in vivo. The proposed NC will be used for cancer imaging in ovarian tumor bearing mice (TCCN) and for tracking single breast cancer metastasis homing to the brain (CCNE-T). The successful completion of the project will provide a potent nano-tool for cancer detection and, possibly, for shedding new lights on the dynamics of cancer metastasis.
Pilot Program Grants:
15 proposals received; 2 awarded by the review committee
- MUCI targeted plasmonic nanobubble theronostics for pancreatic cancer (PI: Pamela E. Constantinou Papadopoulos, Ph.D., Rice University)
- Programming Logic into Virus Nanoparticles for Targeted shRNA Delivery to Ovarian Cancer Cells (PI: Junghae Suh, Ph.D., Rice University)