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188. Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials

Author

Yuan, Hushan, Wilks, Moses Q., El Fakhri, Georges, Normandin, Marc D., Kaittanis, Charalambos, and Josephson, Lee

Subjects
Biology and Life Sciences, Immunology, Immunity, Humoral Immunity, Humoral Immune Response, Medicine and Health Sciences, Biochemistry, Proteins, Protamines, Physical Sciences, Chemistry, Chemical Compounds, Hydrocarbons, Alkynes, Azides, Engineering and Technology, Nanotechnology, Nanoparticles, Separation Processes, Filtration, Ultrafiltration, Cell Biology, Cell Physiology, Cell Binding
Abstract

A key advantage of nanomaterials for biomedical applications is their ability to feature multiple small reporter groups (multimodality), or combinations of reporter groups and therapeutic agents (multifunctionality), while being targeted to cell surface receptors. Here a facile combination of techniques for the syntheses of multimodal, targeted nanoparticles (NPs) is presented, whereby heat-induced-radiolabeling (HIR) labels NPs with radiometals and so-called click chemistry is used to attach bioactive groups to the NP surface. Click-reactive alkyne or azide groups were first attached to the nonradioactive clinical Feraheme (FH) NPs. Resulting “Alkyne-FH” and “Azide-FH” intermediates, like the parent NP, tolerated 89Zr labeling by the HIR method previously described. Subsequently, biomolecules were quickly conjugated to the radioactive NPs by either copper-catalyzed or copper-free click reactions with high efficiency. Synthesis of the Alkyne-FH or Azide-FH intermediates, followed by HIR and then by click reactions for biomolecule attachment, provides a simple and potentially general path for the synthesis of multimodal, multifunctional, and targeted NPs for biomedical applications.

Published
2017
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189. Theranostic Nucleic Acid Binding Nanoprobe Exerts Anti-inflammatory and Cytoprotective Effects in Ischemic Injury

Author

Chen, Howard H., Yuan, Hushan, Cho, Hoonsung, Feng, Yan, Ngoy, Soeun, Kumar, Anand T. N., Liao, Ronglih, Chao, Wei, Josephson, Lee, and Sosnovik, David E.

Subjects
DNA, RNA, Inflammation, Ischemia, Nanoprobe, Imaging.
Abstract

Extracellular nucleic acids are proinflammatory molecules that have been implicated in a diverse range of diseases. We report here the development of a multivalent nucleic acid scavenging nanoprobe, where the fluorochrome thiazole orange (TO) is conjugated to a polymeric 40 kDa dextran carrier. Dextran-TO (Dex-TO) has nanomolar affinity for mammalian and bacterial nucleic acids and attenuates the production of inflammatory cytokines from activated macrophages exposed to DNA and RNA. Mice with myocardial ischemia reperfusion that were treated with Dex-TO showed a decrease in myocardial macrophage infiltration at 24 hours (p<0.05) and a decrease in infarct size (18% ± 9%, p<0.01) on day 7. Dex-TO allows sites of injury to be identified with fluorescence imaging, while simultaneously exerting an anti-inflammatory and cytoprotective effect. Dex-TO could be of significant diagnostic and therapeutic (theranostic) utility in a broad range of conditions including ischemia, trauma, burns, sepsis and autoimmune disease.

Published
2017
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