Gold nanoparticles and cancer: Detection, diagnosis and therapy

Abstract

Gold nanoparticles (AuNPS) represent one of the most studied classes of nanomaterials for biomedical applications, especially in the field of cancer research. In fact, due to their unique properties and high versatility, they can be exploited under all aspects connected to cancer management, from early detection to diagnosis and treatment. AuNPs have thus been tested with amazing results as biosensors, contrast agents, therapeutics. Their importance as potent theranostics is undoubted, but the translation to clinical practice has been hampered by a series of aspects, such as the unclear toxicity in humans and the lack of thorough studies on reliable animal models. Still, their potential action is so appealing and the results so impressive that an outstanding number of papers is being published every year, with the consequence that any review on this topic becomes obsolete within a few months. Here we would like to report the latest findings on AuNPs research addressing all their functions as theranostic agents.

Introduction

Engineered nanomaterials massively emerged about two decades ago, at the beginning of the third millennium, and revolutionized most of the technological and scientific fields [1]. Human health was not an exception, and the term “nanomedicine” [2] was coined to describe the application of nanoscience and nanotechnology to the therapy, diagnosis and prevention of diseases, especially cancer, for which the superiority of nanomedicine over conventional treatments was immediately recognized. In fact, traditional anticancer therapies lack in selectivity and specificity, affecting healthy cells as much as sick ones. Nanomaterials, instead, not only can be designed for tumour targeting, drug delivery and enhancing conventional cancer immunotherapy, but also to create biosensors, increase imaging performances, repair damaged tissues: they can act both as therapeutic and diagnostic tools, for which another new term was coined: “theranostics” [3,4]. This would lead to the development of the so-called “personalized medicine”, one of the most crucial challenges for the future of healthcare [5].

Despite the so many evident benefits brought to the biomedical field by nanomaterials, only a few of them made it to the clinical trials [6], and an even lower number were clinically approved and commercialised, such as liposomes and iron nanoparticles for NMR imaging (MRI) or photodynamic therapy [7,8]. The key aspect in the nearly systematic failure of nanomaterials in clinical translation, lies in the almost chronical lack of any assessment of the potential nanodrug under the pharmacological point of view, that is, almost no evaluation of its intrinsic toxicity, solubility, stability in physiological conditions, bioavailability, proneness to biotransformations etc., is carried out before its application to in vitro cell cultures or in vivo models. Nevertheless, the increasing incidence of cancer and other neoplasms demands that these new formulations could find real, safe and widespread application, thus their design should take in consideration also the abovementioned properties, including their potential toxicity, about which researchers are still debating, and the need of improving traditional testing on animal models [[9], [10], [11]].

Anyway, among the highly promising nanomaterials, gold nanoparticles are one of the most extensively studied, due to their outstanding and probably unique physical, chemical, optical and electronic properties, that make them suitable for the creation of highly multifunctional platforms for biochemical applications [12,13]. Moreover, their shape can be modelled into a variety of forms, such as nanocages, nanoboxes, nanorods, nanowires, hollow nanospheres, and nanoflowers (also called nanourchins or nanostars), each with its peculiar characteristics, behaviour and applications. They can be made out of pure gold, form composites (coated with polymers, such as polyethilenglycol (PEG), and other organic compounds) or be “doped” with other metals (Ag, Se, Mo, Mn, Pt, Fe₃O₄, for instance) to give new hybrid materials which can be further capped, functionalised or conjugated with drugs or other molecules for cell targeting and drug delivery. As theranostics, they show high direct anticancer activity, but are also active in the photothermal/photodynamic therapy, in biosensing and immunoassay, as contrast or imaging agents, or nanozymes [12].

Here we would like to give an account of the most recent findings and applications of gold nanoparticles in the field of cancer detection, diagnosis and treatment. In less than five years (2017-early 2021) more than 4000 articles and reviews have been published on this topic, nearly one thousand per year (sources: Scopus, Pubmed, Google Scholar), showing an impressive interest for these nanostructures and the remarkable efforts done to carry out research in the diagnosis and treatment of cancer with gold nanotechnology, resulting in a rapid “outdating” even of the most recent papers.

For evident reasons, it will not be possible to include all these works in the present review, that will be necessarily limited to the last 2–3 years. Therefore, the authors want to apologize for those that will be inevitably excluded.