Synthesis and In Vitro Evaluation of Gold Nanoparticles Functionalized with Thiol Ligands for Robust Radiolabeling with 99mTc.

Adamantia Apostolopoulou,Aristeidis Chiotellis,Penelope Bouziotis,Charalampos Tsoukalas,Fotis Kapiris,Konstantina Makrypidi,Przemysław Koźmiński,Evangelia-Alexandra Salvanou,Ioannis C Pirmettis,Maria Paravatou-Petsotas,Minas Papadopoulos

doi:10.3390/nano11092406

Abstract

Radiolabeled gold nanoparticles (AuNPs) have been widely used for cancer diagnosis and therapy over recent decades. In this study, we focused on the development and in vitro evaluation of four new Au nanoconjugates radiolabeled with technetium-99m (99mTc) via thiol-bearing ligands attached to the NP surface. More specifically, AuNPs of two different sizes (2 nm and 20 nm, referred to as Au(2) and Au(20), respectively) were functionalized with two bifunctional thiol ligands (referred to as L1H and L2H). The shape, size, and morphology of both bare and ligand-bearing AuNPs were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. In vitro cytotoxicity was assessed in 4T1 murine mammary cancer cells. The AuNPs were successfully radiolabeled with 99mTc-carbonyls at high radiochemical purity (>95%) and showed excellent in vitro stability in competition studies with cysteine and histidine. Moreover, lipophilicity studies were performed in order to determine the lipophilicity of the radiolabeled conjugates, while a hemolysis assay was performed to investigate the biocompatibility of the bare and functionalized AuNPs. We have shown that the functionalized AuNPs developed in this study lead to stable radiolabeled nanoconstructs with the potential to be applied in multimodality imaging or for in vivo tracking of drug-carrying AuNPs.

Highlights

Nanoparticles are materials with dimensions at the nanometer scale (1–100 nm) and over the last decades have been widely used in theranostic applications, playing an effective role in the diagnosis and therapy of cancer by offering multiple possibilities in oncology [1]
Gold nanoparticles are synthesized by various methods, including the reduction of gold ions (Au3+ ) to produce gold atoms (Au0 )
Nuclear magnetic resonance (NMR) spectra were recorded in DMSO-d6 on a Bruker Avance DRX 500 MHz spectrometer at room temperature

Summary

Introduction

Nanoparticles are materials with dimensions at the nanometer scale (1–100 nm) and over the last decades have been widely used in theranostic applications, playing an effective role in the diagnosis and therapy of cancer by offering multiple possibilities in oncology [1]. The aim of nanotechnology is to allow efficient accumulation of the nanodrug in the target organ or tissue, regardless of the method and the route of administration, while limiting unwanted toxic effects due to the administration of high concentrations of conventional anticancer drugs. Gold nanoparticles (AuNPs) have been extensively investigated for the development of dual-modality imaging agents, as well as for theranostic applications due to their unique physicochemical properties, ease of surface functionalization with different chemical entities, low toxicity, and biocompatibility. They present high sensitivity and Nanomaterials 2021, 11, 2406. AuNPs can reach the disease site via active targeting, where targeting ligands (such as peptides or monoclonal antibodies) attached to the nanoparticle surface recognize specific receptors overexpressed on the surface of tumor cells, resulting in enhanced accumulation in the targeted organ [7,8]

Methods

Results

Conclusion