title: Click-assembled, oxygen-sensing nanoconjugates for depth-resolved, near-infrared imaging in a 3D cancer model.
abstract: Hypoxia is an important contributing factor to the development of drug-resistant cancer, yet few nonperturbative tools exist for studying oxygenation in tissues. While progress has been made in the development of chemical probes for optical oxygen mapping, penetration of such molecules into poorly perfused or avascular tumor regions remains problematic. A click-assembled oxygen-sensing (CAOS) nanoconjugate is reported and its properties demonstrated in an in vitro 3D spheroid cancer model. The synthesis relies on the sequential click-based ligation of poly(amidoamine)-like subunits for rapid assembly. Near-infrared confocal phosphorescence microscopy was used to demonstrate the ability of the CAOS nanoconjugates to penetrate hundreds of micrometers into spheroids within hours and to show their sensitivity to oxygen changes throughout the nodule. This proof-of-concept study demonstrates a modular approach that is readily extensible to a wide variety of oxygen and cellular sensors for depth-resolved imaging in tissue and tissue models.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, CNY 149-3210, 13th Street, Charlestown, MA 02129 (USA); Harvard University Program in Biophysics, Building C2 Room 112, 240 Longwood Avenue, Boston, MA 02115 (USA); Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue E25-519, Cambridge, MA 02139 (USA).
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Nichols
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roussakis
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Klein
authors.forename: Conor L
authors.initials: CL
authors.lastname: Evans
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D057930:Click Chemistry; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods*; D058726:Nanoconjugates / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D011877:Radionuclide Imaging
chemical_list: D000970:Antineoplastic Agents; D058726:Nanoconjugates
keywords: cancer; click chemistry; dendrimers; imaging agents; nanotechnology