Abstract

Citrate-capped gold nanoparticles (AuNPs) were functionalized with three distinct antitumor gold(III) complexes, e.g., [Au(N,N)(OH)2][PF6], where (N,N)=2,2′-bipyridine; [Au(C,N)(AcO)2], where (C,N)=deprotonated 6-(1,1-dimethylbenzyl)-pyridine; [Au(C,N,N)(OH)][PF6], where (C,N,N)=deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine, to assess the chance of tracking their subcellular distribution by atomic force microscopy (AFM), and surface enhanced Raman spectroscopy (SERS) techniques. An extensive physicochemical characterization of the formed conjugates was, thus, carried out by applying a variety of methods (density functional theory—DFT, UV/Vis spectrophotometry, AFM, Raman spectroscopy, and SERS). The resulting gold(III) complexes/AuNPs conjugates turned out to be pretty stable. Interestingly, they exhibited a dramatically increased resonance intensity in the Raman spectra induced by AuNPs. For testing the use of the functionalized AuNPs for biosensing, their distribution in the nuclear, cytosolic, and membrane cell fractions obtained from human lymphocytes was investigated by AFM and SERS. The conjugates were detected in the membrane and nuclear cell fractions but not in the cytosol. The AFM method confirmed that conjugates induced changes in the morphology and nanostructure of the membrane and nuclear fractions. The obtained results point out that the conjugates formed between AuNPs and gold(III) complexes may be used as a tool for tracking metallodrug distribution in the different cell fractions.

Highlights

  • Among the large number of gold(III) complexes synthesized so far with the goal to overcome the toxic side effects of platinum(II) drugs in anticancer treatment [1,2], the compounds having aromatic N-containing heterocycles as ligands have gained special interest, as such ligands greatly increase the stability of these metal compounds under physiological conditions [3,4,5,6]

  • The functionalization of 30 nm citrate-capped AuNPs by the series of mononuclear antitumor gold(III) complexes ([Au(C,N,N)(OH)][PF6], [Au(N,N)(OH)2][PF6] and [Au(C,N)(AcO)2]) led to the formation of stable nanostructured assemblies that allow the tracking of their subcellular distribution in cell fractions using the atomic force microscopy (AFM) and SERS techniques

  • The formation of gold(III) complex/AuNPs conjugates, and their physicochemical properties were characterized by various methods (DFT calculations, UV/Vis spectrophotometry, AFM, Raman spectroscopy, and SERS)

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Summary

Introduction

Among the large number of gold(III) complexes synthesized so far with the goal to overcome the toxic side effects of platinum(II) drugs in anticancer treatment [1,2], the compounds having aromatic N-containing heterocycles as ligands have gained special interest, as such ligands greatly increase the stability of these metal compounds under physiological conditions [3,4,5,6].

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