title: Label-free visualization of nilotinib-functionalized gold nanoparticles within single mammalian cells by C60- SIMS imaging.
abstract: Obtaining a comprehensive grasp of the behavior and interaction of pharmaceutical compounds within single cells provides some of the fundamental details necessary for more effective drug development. In particular, the changes ensuing in the carrier, drug, and host environment in targeted drug therapy applications must be explored in greater detail, as these are still not well understood. Here, nilotinib-functionalized gold nanoparticles are examined within single mammalian cells with use of imaging cluster secondary ion mass spectrometry in a model study designed to enhance our understanding of what occurs to these particles once that have been internalized. Nilotinib, several types of gold nanoparticles, and the functionalized combination of the two were surveyed and successfully imaged within single cells to determine uptake and performance. Both nilotinib and the gold particle are able to be distinguished and visualized in the functionalized nanoparticle assembly within the cell. These compounds, while both internalized, do not appear to be present in the same pixels of the chemical image, indicating possible cleavage of nilotinib from the particle after cell uptake. The method provided in this work is a direct measurement of uptake and subcellular distribution of an active drug and its carrier within a framework. The results obtained from this study have the potential to be applied to future studies to provide more effective and specific cellular delivery of a relevant pharmaceutical compound.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, 104 Chemistry Building, University Park, PA, 16802, USA. blooman06@gmail.com.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Bloom
authors.affiliation: Department of Chemistry, The Pennsylvania State University, 104 Chemistry Building, University Park, PA, 16802, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.affiliation: Nanopartz Inc., 146 Barberry Place, Loveland, CO, 80537, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Schoen
authors.affiliation: Department of Chemistry, The Pennsylvania State University, 104 Chemistry Building, University Park, PA, 16802, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Winograd
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000032:analysis*; D016503:Drug Delivery Systems; D006046:Gold / Q000032:analysis*; D053768:Metal Nanoparticles / Q000032:analysis*; D051379:Mice; D010316:Particle Size; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000067996:RAW 264.7 Cells; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011743:Pyrimidines; D006046:Gold; C498826:nilotinib
keywords: Gold nanoparticles; Nilotinib; Secondary ion mass spectrometry; Targeted drug therapy