title: Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials.
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.
authors.affiliation: Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, Charlestown, Massachusetts, United States of America.
authors.forename: Hushan
authors.identifier: http://orcid.org/0000-0002-2243-7903
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, Charlestown, Massachusetts, United States of America.
authors.forename: Moses Q
authors.initials: MQ
authors.lastname: Wilks
authors.affiliation: Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, Charlestown, Massachusetts, United States of America.
authors.forename: Georges
authors.initials: G
authors.lastname: El Fakhri
authors.affiliation: Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, Charlestown, Massachusetts, United States of America.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.affiliation: Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, Charlestown, Massachusetts, United States of America.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Kaittanis
authors.affiliation: Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, Charlestown, Massachusetts, United States of America.
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
mesh_terms: D057930:Click Chemistry / Q000379:methods*; D006358:Hot Temperature; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry*