This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-CA-116: Physical Sciences and Cellular Mechanics. We will develop analytical imaging capabilities with complementary nanoparticle probes to measure the viscoelastic properties of cells and tissues in a noninvasive manner. These capabilities will be applied toward understanding biomechanical factors on tumor growth dynamics. Near-infrared (NIR) absorbing Au nanoparticles with magnetic cores will serve as multimodal contrast agents for multiphoton imaging and for magnetomotive optical coherence tomography (MM-OCT) and elastography (MM-OCE), to characterize viscoelastic changes in tumor cells and tissues as a function of their development. Tumor cells will be laden with nanoprobes and cocultured with fibroblasts or macrophages for in vitro multimodal imaging with MM-OCE. Tumor xenografts will also be grown in mice from nanoprobe-laden tumor cells, then excised for ex vivo imaging with results collated with conventional metrics of tumor development (i.e., visual inspection and histology). We anticipate this approach can reveal critical biomechanical differences in the development of invasive carcinomas, in which cells undergo transformations from turgid states with high tensile strength to plastic and deformable states associated with migration and extravasation.
Our Specific Aims are as follows: 1) Construction of an integrated optical platform for optical coherence tomography (OCT) and elastography (OCE), for noninvasive imaging of tumor tissues with cellular resolution; 2) Fabrication of nanoprobes that combine plasmon resonance with magnetomotive activity, to generate unique NIR signatures for 3D imaging and elastography; 3) Optimization and deployment of the multimodal imaging platform for simultaneous structural imaging and viscoelastic profiling of nanoprobe-laden tumor cells and excised tumor tissues.
Investigating Tumor Growth Dynamics with Multimodal Contrast Agents and Optical Coherence Elastography: Narrative We will develop a multimodal optical imaging platform complemented with magnetomotive, NIR- active nanoprobes, for noninvasive measurements of the viscoelastic properties of cells and tissues. Tumor cells laden with nanoprobes will be co-cultured with fibroblasts or macrophages for in vitro multimodal imaging. Tumor xenografts will also be grown in mice from nanoprobe- laden tumor cells, then excised for ex vivo imaging. These studies will increase our understanding of biomechanical factors on tumor growth dynamics
|Mehtala, Jonathan G; Wei, Alexander (2014) Nanometric resolution in the hydrodynamic size analysis of ligand-stabilized gold nanorods. Langmuir 30:13737-43|
|Mehtala, Jonathan G; Zemlyanov, Dmitry Y; Max, Joann P et al. (2014) Citrate-stabilized gold nanorods. Langmuir 30:13727-30|
|Mehtala, Jonathan G; Torregrosa-Allen, Sandra; Elzey, Bennett D et al. (2014) Synergistic effects of cisplatin chemotherapy and gold nanorod-mediated hyperthermia on ovarian cancer cells and tumors. Nanomedicine (Lond) 9:1939-55|
|Boulos, Stefano P; Prigozhin, Maxim B; Liu, Yuan et al. (2013) The Gold Nanorod-Biology Interface: From Proteins to Cells to Tissue. Curr Phys Chem 3:|
|Tu, H; Liu, Y; Lægsgaard, J et al. (2012) Cross-validation of theoretically quantified fiber continuum generation and absolute pulse measurement by MIIPS for a broadband coherently controlled optical source. Appl Phys B 106:379-384|
|Tu, Haohua; Liu, Yuan; Liu, Xiaomin et al. (2012) Nonlinear polarization dynamics in a weakly birefringent all-normal dispersion photonic crystal fiber: toward a practical coherent fiber supercontinuum laser. Opt Express 20:1113-28|
|Wei, Alexander; Mehtala, Jonathan G; Patri, Anil K (2012) Challenges and opportunities in the advancement of nanomedicines. J Control Release 164:236-46|
|Xia, Wei; Song, Hyon-Min; Wei, Qingshan et al. (2012) Differential response of macrophages to core-shell Fe3O4@Au nanoparticles and nanostars. Nanoscale 4:7143-8|
|Tang, Zhao; Wei, Alexander (2012) Fabrication of anisotropic metal nanostructures using innovations in template-assisted lithography. ACS Nano 6:998-1003|
|Liu, Yuan; Tu, Haohua; Benalcazar, Wladimir A et al. (2012) Multimodal Nonlinear Microscopy by Shaping a Fiber Supercontinuum From 900 to 1160 nm. IEEE J Sel Top Quantum Electron 18:|
Showing the most recent 10 out of 29 publications