Nanotechnology holds promise for new treatments for disease in man. Nanoparticle-based approaches offer the possibility of significant advances over current clinical methods accommodating multiple therapeutic, imaging, targeting or other effector functions within each nanoplatform. while improving the pharmacological properties of imaging agents and drugs The multifunctional nature of nanoplatforms is therefore well-suited for the diagnosis and treatment of complex diseases involving multiple physiological compartments, such as cancer. The overall objective of project 3 is to characterize the impact of vascular targeting on the accumulation of new programmable """"""""smart"""""""" nanoplatforms (SNaPs) within tumors.
AIM 1 will examine the characterize how targeting nanoplatforms to oncofetal integrin receptors - expressed on tumors and tumor vasculature - leads to accumulation within these sites. These studies will focus on understanding the impact of affinity and avidity on the ultimate accumulation of nanoparticle within the target site.
In AIM 2. we will assess targeting of nanoplatforms which undergo spontaneous self-assembly on a """"""""honeycomb"""""""" core, based on host-guest chemical interactions. Assembly is dependent upon integration of polyethyleneglycol polymer (PEG)-conjugated molecular guests. The distal terminus of the PEG polymers are pre-conjugated to """"""""programmable"""""""" elements, such as targeting or imaging agents. The targeting and stability of the SNaPs will be tested against conventional nanoparticles.
Both AIMS 1 &2 will employ MRI of avian tumor models and the dorsal window preparation of optically imaged mice with dual reporter (optical & Gd) bearing nanoparticles.
AIM 3. The capacity to incorporate multiple targeting elements into the SNaPs by simple ratiometric combination of the host platform and the guest-anchored moieties will be used to evaluate whether combinatorial approaches at targeting - using ligands for two different receptors on the target cell - offers any increase in specificity over singly targeted. Finally, in AIM 4. we will extend the studies from simply imaging accumulation at particle sites to testing whether multifunctional, imagable nanoparticles can detect nascent tumors in genetic preclinical models of disease. The studies will employ Optical and MR imaging of mouse models of subcutaneous tumor growth and metastasis, and spontaneous murine models of tumor development. We believe that these studies should lay the groundwork for a new generation of easily programmed, multifunctional nanoplatforms, amenable to the imaging and possibly treatment of malignancy in human patients. Such particles represent an important first step towards the development of """"""""on site"""""""" programmable and personalized, but mass-producible, diagnostic/therapeutic products.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Special Emphasis Panel (ZCA1-SRRB-9)
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University of California San Diego
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Qin, Zhengtao; Hoh, Carl K; Hall, David J et al. (2015) A tri-modal molecular imaging agent for sentinel lymph node mapping. Nucl Med Biol 42:917-22
Malone, Christopher D; Olson, Emilia S; Mattrey, Robert F et al. (2015) Tumor Detection at 3 Tesla with an Activatable Cell Penetrating Peptide Dendrimer (ACPPD-Gd), a T1 Magnetic Resonance (MR) Molecular Imaging Agent. PLoS One 10:e0137104
Goodwin, Andrew P; Nakatsuka, Matthew A; Mattrey, Robert F (2015) Stimulus-responsive ultrasound contrast agents for clinical imaging: motivations, demonstrations, and future directions. Wiley Interdiscip Rev Nanomed Nanobiotechnol 7:111-23
Sicklick, Jason K; Leonard, Stephanie Y; Babicky, Michele L et al. (2014) Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor. J Transl Med 12:41
Liss, Michael A; Farshchi-Heydari, Salman; Qin, Zhengtao et al. (2014) Preclinical evaluation of robotic-assisted sentinel lymph node fluorescence imaging. J Nucl Med 55:1552-6
Hosseini, Ava; Baker, Jennifer L; Tokin, Christopher A et al. (2014) Fluorescent-tilmanocept for tumor margin analysis in the mouse model. J Surg Res 190:528-34
Liberman, Alexander; Wu, Zhe; Barback, Christopher V et al. (2014) Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound. J Surg Res 190:391-8
Felsen, Csilla N; Savariar, Elamprakash N; Whitney, Michael et al. (2014) Detection and monitoring of localized matrix metalloproteinase upregulation in a murine model of asthma. Am J Physiol Lung Cell Mol Physiol 306:L764-74
Liss, Michael A; Stroup, Sean P; Qin, Zhengtao et al. (2014) Robotic-assisted fluorescence sentinel lymph node mapping using multimodal image guidance in an animal model. Urology 84:982.e9-14
Liberman, Alexander; Wu, Zhe; Barback, Christopher V et al. (2013) Color Doppler ultrasound and gamma imaging of intratumorally injected 500 nm iron-silica nanoshells. ACS Nano 7:6367-77

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