Abstract

The cellular uptake of gold nanoparticles (AuNPs) may (or may not) affect their speciation, but information on the chemical forms in which the particles exist in the cell remains obscure. An analytical method based on the use of capillary electrophoresis hyphenated with inductively coupled plasma mass spectrometry (ICP-MS) has been proposed to shed light on the intracellular processing of AuNPs. It was observed that when being introduced into normal cytosol, the conjugates of 10–50 nm AuNPs with albumin evolved in human serum stayed intact. On the contrary, under simulated cancer cytosol conditions, the nanoconjugates underwent decomposition, the rate of which and the resulting metal speciation patterns were strongly influenced by particle size. The new peaks that appeared in ICP-MS electropherograms could be ascribed to nanosized species, as upon ultracentrifugation, they quantitatively precipitated whereas the supernatant showed only trace Au signals. Our present study is the first step to unravel a mystery of the cellular chemistry for metal-based nanomedicines.

Highlights

  • Gold nanoparticles (AuNPs) are widely researched as multifunctional theranostic agents, having, among other possible biomedical functions, the capability to exert anticancer efficacy by interacting with and altering tumor cells [1,2,3,4]

  • The analytical methodology used in our studies [14,15,16] is based on coupling capillary electrophoresis (CE) to inductively coupled plasma mass spectrometry

  • We decided to employ in the following experiments the HEPES buffer (4-(2-hydroxyethyl)piperazine-1ethanesulfonic acid) of pH 7.4 that was successfully utilized for monitoring the speciation changes of AuNPs in human serum [14]

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Summary

Introduction

Gold nanoparticles (AuNPs) are widely researched as multifunctional theranostic agents, having, among other possible biomedical functions, the capability to exert anticancer efficacy by interacting with and altering tumor cells [1,2,3,4]. In contrast to metal-based drugs, for which the mechanisms of action have been at least in part elucidated, knowledge of the events involved in the cellular processing of AuNPs is limited. Given the intravenous route of administration, the foremost changes in the chemical state of AuNPs are due to interaction with proteins in the circulatory system [10,11,12]. It has been confirmed that for AuNPs engineered with different shapes, sizes, and surface modifications, the formation of the protein corona in human serum and, the biological identity and response strongly depend on each of these constructive attributes [13,14,15,16,17,18]. The analytical methodology used in our studies [14,15,16] is based on coupling capillary electrophoresis (CE) to inductively coupled plasma mass spectrometry

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