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Modular assembly of surface functionalized core-shell nanoparticle probes for multimodal imaging including spectral CT

2016; Frontiers Media; Volume: 4; Linguagem: Inglês

10.3389/conf.fbioe.2016.01.00044

2296-4185

Nallathamby Prakash, Mcginnity Tracie, Curtis Tyler, Vargo-Gogola Tracy, Cowden-Dahl Karen, Roeder Ryan,

Optical Imaging and Spectroscopy Techniques

Event Abstract Back to Event Modular assembly of surface functionalized core-shell nanoparticle probes for multimodal imaging including spectral CT Prakash Nallathamby1, Tracie L. Mcginnity1, Tyler Curtis1, Tracy Vargo-Gogola2, Karen Cowden-Dahl3 and Ryan K. Roeder1 1 University of Notre Dame, MRB-Aerospace and Mechanical Engineering, United States 2 Indiana University School of Medicine, Director of Curriculum Development, United States 3 Indiana University School of Medicine-South Bend, Biochemistry and Molecular Biology, United States Introduction: Contrast-enhanced computed tomography (CT) and spectral (color) CT have the potential to enable molecular imaging in CT [1]. However, there is a lack of contrast agents designed to fully leverage the capabilities of spectral CT. Therefore, the objective of this study was to develop a modular approach to design a spectral library of core-shell nanoparticle contrast agents, which will have broad applications in biomedical imaging due to potential for multi-modal imaging (e.g., fluorescence, MRI, X-ray, plasmonic resonance), dosed delivery of therapeutics and active targeting through molecular surface functionalization. Materials and Methods: Gadolinium oxide (Gd2O3), hafnium oxide (HfO2) and gold (Au) core compositions were prepared at a common size (12-15 nm) using chemical and sol-gel synthesis (Fig. 1A) [2],[3]. Nanoparticle (NP) cores were encapsulated in a silica shell with controlled thickness of 1-15 nm, using polymer shells or Igepal (Fig.1B) [4],[5]. Controlled silica shell formation enabled controlled loading of fluorescent molecules and provided a common platform for molecular surface functionalization using silane chemistry. Antibodies and other small molecules were efficiently conjugated to the nanoparticles using EDC/NHS chemistry [6]. The bioactivity and orientation of IgG antibodies conjugated to NPs were confirmed through agglomeration assays and electron microscopy. Results and Discussion: Silica shell formation was robust for a variety of NP core compositions. The silica shell thickness was able to be tailored by controlling the molecular weights and concentration of the priming polymer (PVP) or non-ionic detergents (Igepal) that were employed (Fig.1B). The yield of as prepared core-shell NPs was consistently > 99% in solution. The silica shell was able to be volume loaded with a controlled number of fluorophores for dual mode imaging and validation of NP delivery and concentrations in vivo. Core-shell NP contrast agents were imaged by conventional CT, spectral CT and MRI in imaging phantoms and in murine models in vivo. Antibodies were readily conjugated to the silica shell (Fig. 2), enabling immunotargeting of cells and tissues for multimodal molecular imaging. Conclusions: Core shell NPs with various compositions were prepared using a modular approach that enabled encapsulation of the core with a tunable (1-15 nm) silica shell thickness, facile molecular surface functionalization, controlled loading of fluorophores and multi-modal imaging (X-ray, MRI, fluorescence and plasmonic resonance). NSF DMR-1309587; St. Joseph Regional Medical Center; Indiana CTSI (NIH RR025761); Harper Cancer Research Institute - ABC Grant; Kelly Cares FoundationReferences:[1] (a) Anderson NG, et al., Contrast Media Molecular Imaging 2014, 9, 3 (b) Cole LE, et al., Nanomedicine 2015, 10, 321[2] R. Ramos-Gonzáleza, et al., Applied Surface Science 2012, 258, 6034[3] Jong Hui Kim, et al., J. Nanoparticle Research 2011, 13, 2311[4] Yu Han, et al., Langmuir 2008, 24, 5842[5] Noah J. J. Johnson, et al., Nanoscale, 2010, 2, 771[6] (a) Huang T, et al., Analytical Chemistry 2007, 79, 7708 (b) Huang T, et al., J. American Chemical Society 2008, 130, 17095 Keywords: nanoparticle, theranostic, Imaging method, targeting delivery Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Bioconjugates Citation: Nallathamby P, Mcginnity TL, Curtis T, Vargo-Gogola T, Cowden-Dahl K and Roeder RK (2016). Modular assembly of surface functionalized core-shell nanoparticle probes for multimodal imaging including spectral CT. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00044 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers' terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Prakash Nallathamby Tracie L Mcginnity Tyler Curtis Tracy Vargo-Gogola Karen Cowden-Dahl Ryan K Roeder Google Prakash Nallathamby Tracie L Mcginnity Tyler Curtis Tracy Vargo-Gogola Karen Cowden-Dahl Ryan K Roeder Google Scholar Prakash Nallathamby Tracie L Mcginnity Tyler Curtis Tracy Vargo-Gogola Karen Cowden-Dahl Ryan K Roeder PubMed Prakash Nallathamby Tracie L Mcginnity Tyler Curtis Tracy Vargo-Gogola Karen Cowden-Dahl Ryan K Roeder Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.