Assessing the Intracellular Integrity of Phosphine‐Stabilized Ultrasmall Cytotoxic Gold Nanoparticles Enabled by Fluorescence Labeling. Issue 24 (18th November 2016)

• Record Type: Journal Article
• Authors: Broda, Janine; Küster, Andrea; Westhues, Stefan; Fahrenkamp, Dirk; Vogg, Andreas T. J.; Steitz, Julia; Mottaghy, Felix M.; Müller‐Newen, Gerhard; Simon, Ulrich
• Is Part Of: Advanced healthcare materials. Volume 5:Issue 24(2016)
• Page Start: 3118
• Page End: 3128
• Publication Date: 2016-11-18
• Subjects: cellular uptake -- fluorescence -- gold nanoparticles -- TPPMS; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201600892
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract : As the size of nanoparticles (NPs) is in the range of biological molecules and subcellular structures, they provide new perspectives in biomedicine. This work presents studies concerning the cellular uptake and distribution of phosphine‐stabilized cytotoxic 1.4 nm sized AuNPs and their probable degradation during this process. Therefore, ultrasmall phosphine‐stabilized AuNPs are modified by linking a fluorophore covalently to the ligand shell. Monitoring the fluorescence on a cellular level by means of flow cytometry and confocal laser scanning microscopy allows determining the fate of the ligand shell during AuNP cell internalization, due to the fact that the fluorescence of a fluorophore bound near to the AuNP surface is quenched. Cell fractionation is conducted in order to quantify the AuNP content at the cell membrane, in the cytoplasm, and the cell nucleus. The incubation of cells with the fluorophore‐modified AuNPs reveals a partial loss of the ligand shell upon AuNP cell interaction, evident by the emerging fluorescence signal. This loss is the precondition to unfold high AuNP cytotoxicity. Together with their significantly different biodistribution and enhanced circulation times compared to larger AuNPs, the findings demonstrate the high potential of ultrasmall AuNPs for drug development or therapy. Abstract : The cellular uptake and intracellular distribution of phosphine‐stabilized cytotoxic 1.4 nm sized gold nanoparticles (AuNPs) are investigated. Therefore, well known ultrasmall AuNPs are modified by linking a fluorophore covalently to the ligand shell, which leads to quenching. Upon cellular uptake, the ligands are released, monitored by the evolution of the fluorescence with confocal laser scanning microscopy.