Label-free visualization of nilotinib-functionalized gold nanoparticles within single mammalian cells by C60- SIMS imaging
- 343 Downloads
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.
KeywordsSecondary ion mass spectrometry Targeted drug therapy Nilotinib Gold nanoparticles
The generous support and donation of compounds and technical support by Novartis Pharmaceuticals (David Six and Thomas Krucker) is gratefully acknowledged. This project was financially supported by the National Institutes of Health (grant no. 5R01 GM113746-22).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Tufts Center for the Study of Drug Development. Outlook 2015. Boston: Tufts Center for the Study of Drug Development; 2015.Google Scholar
- 3.Morgan P, Van der Graaf PH, Arrowsmith J, Feltner DE, Drummond KS, Wegner CD, et al. Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving phase II survival. Drug Discov Today. 2012;17(9-10):419–24. doi: 10.1016/j.drudis.2011.12.020.CrossRefGoogle Scholar
- 11.Dasgupta A (2012) In: Dasgupta A (eds) Therapeutic drug monitoring: newer drugs and biomarkers. London: Academic; 2012. p. ix-XGoogle Scholar
- 24.Reinwald M, Schleyer E, Kiewe P, Blau IW, Burmeister T, Pursche S, et al. Efficacy and pharmacologic data of second-generation tyrosine kinase inhibitor nilotinib in BCR-ABL-positive leukemia patients with central nervous system relapse after allogeneic stem cell transplantation. Biomed Res Int. 2014;2014:637059. doi: 10.1155/2014/637059.CrossRefGoogle Scholar
- 36.Abumiya M, Takahashi N, Niioka T, Kameoka Y, Fujishima N, Tagawa H, et al. Influence of UGT1A1*6,*27, and*28 Polymorphisms on nilotinib-induced hyperbilirubinemia in Japanese patients with chronic myeloid leukemia. Drug Metab Pharmacokinet. 2014;29(6):449–54. doi: 10.2133/dmpk.DMPK-14-RG-031.CrossRefGoogle Scholar