title: Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy.
abstract: Direct polymerization of an oxaliplatin analogue was used to reproducibly generate amphiphiles in one pot, which consistently and spontaneously self-assemble into well-defined nanoparticles (NPs). Despite inefficient drug leakage in cell-free assays, the NPs were observed to be as cytotoxic as free oxaliplatin in cell culture experiments. We investigated this phenomenon by super-resolution fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion mass spectrometry (NanoSIMS). In combination, these techniques revealed NPs are taken up via endocytic pathways before intracellular release of their cytotoxic cargo. As with other drug-carrying nanomaterials, these systems have potential as cellular delivery vehicles. However, high-resolution methods to track nanocarriers and their cargo at the micro- and nanoscale have been underutilized in general, limiting our understanding of their interactions with cells and tissues. We contend this type of combined optical and isotopic imaging strategy represents a powerful and potentially generalizable methodology for cellular tracking of nanocarriers and their cargo.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Proetto
authors.affiliation: Environmental Molecular Sciences Laboratory (EMSL), Pacific Northwest National Laboratory , Richland, Washington 99354, United States.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Anderton
authors.affiliation: Environmental Molecular Sciences Laboratory (EMSL), Pacific Northwest National Laboratory , Richland, Washington 99354, United States.
authors.forename: Dehong
authors.initials: D
authors.lastname: Hu
authors.affiliation: Environmental Molecular Sciences Laboratory (EMSL), Pacific Northwest National Laboratory , Richland, Washington 99354, United States.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Szymanski
authors.affiliation: Environmental Molecular Sciences Laboratory (EMSL), Pacific Northwest National Laboratory , Richland, Washington 99354, United States.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Zhu
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Patterson
authors.forename: Jacquelin K
authors.initials: JK
authors.lastname: Kammeyer
authors.forename: Lizanne G
authors.initials: LG
authors.lastname: Nilewski
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Rush
authors.forename: Nia C
authors.initials: NC
authors.lastname: Bell
authors.affiliation: Environmental Molecular Sciences Laboratory (EMSL), Pacific Northwest National Laboratory , Richland, Washington 99354, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Evans
authors.affiliation: Environmental Molecular Sciences Laboratory (EMSL), Pacific Northwest National Laboratory , Richland, Washington 99354, United States.
authors.forename: Galya
authors.initials: G
authors.lastname: Orr
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Howell
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Gianneschi
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004705:Endocytosis; D005453:Fluorescence; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004337:Drug Carriers; D009944:Organoplatinum Compounds; D011108:Polymers; D011725:Pyridines; C431073:oxiplatin
keywords: NanoSIMS; SIM; cytotoxicity; drug delivery; drug-loaded nanoparticles; fluorescence; platinum(II) complexes