title: High-throughput quantitation of inorganic nanoparticle biodistribution at the single-cell level using mass cytometry.
abstract: Inorganic nanoparticles (NPs) are studied as drug carriers, radiosensitizers and imaging agents, and characterizing nanoparticle biodistribution is essential for evaluating their efficacy and safety. Tracking NPs at the single-cell level with current technologies is complicated by the lack of reliable methods to stably label particles over extended durations in vivo. Here we demonstrate that mass cytometry by time-of-flight provides a label-free approach for inorganic nanoparticle quantitation in cells. Furthermore, mass cytometry can enumerate AuNPs with a lower detection limit of ∼10 AuNPs (3 nm core size) in a single cell with tandem multiparameter cellular phenotyping. Using the cellular distribution insights, we selected an amphiphilic surface ligand-coated AuNP that targeted myeloid dendritic cells in lymph nodes as a peptide antigen carrier, substantially increasing the efficacy of a model vaccine in a B16-OVA melanoma mouse model. This technology provides a powerful new level of insight into nanoparticle fate in vivo.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Yu-Sang Sabrina
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Prabhani U
authors.initials: PU
authors.lastname: Atukorale
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Kelly D
authors.identifier: 0000-0001-6200-7863
authors.initials: KD
authors.lastname: Moynihan
authors.affiliation: École Polytechnique Fédérale de Lausanne, Institute of Materials and Interfaculty Bioengineering Institute, Lausanne 1015, Switzerland.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bekdemir
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Kavya
authors.initials: K
authors.lastname: Rakhra
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: École Polytechnique Fédérale de Lausanne, Institute of Materials and Interfaculty Bioengineering Institute, Lausanne 1015, Switzerland.
authors.forename: Francesco
authors.identifier: 0000-0003-4635-6080
authors.initials: F
authors.lastname: Stellacci
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.|Ragon Institute of MGH, MIT and Harvard, Charlestown, Cambridge, Massachusetts 02129, USA.
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006046:Gold / Q000032:analysis*; D013058:Mass Spectrometry / Q000379:methods*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D053768:Metal Nanoparticles / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D059010:Single-Cell Analysis / Q000379:methods*; D014018:Tissue Distribution; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D014612:Vaccines; D006046:Gold