Multifunctional Gold Nanocarriers for Cancer Theranostics: From Bench to Bedside and Back Again?

Abstract

After a quarter of century of rapid technological advances, research has revealed the complexity of cancer, a disease intimately related to the dynamic transformation of the genome. However, the full understanding of the molecular onset of this disease is still far from achieved and the search for mechanisms of treatment will follow closely.It is here that Nanotechnology enters the fray offering a wealth of tools to diagnose and treat cancer.It is indisputable that the use of gold nanocarriers has been gaining momentum as vectors for therapy and diagnostic strategies, combining the AuNPs' ease of functionalization with numerous biomolecules, high loading capacity and fast uptake by target cells. In fact, over the last decade nearly 12.000 research papers focusing on multifunctional gold nanocarriers have been published in peer-reviewed journals. Some of the described nanosystems will most likely revolutionize our understanding of biological mechanisms and push forward the clinical practice through their 2 integration in future diagnostics platforms. Nevertheless, very little gave fruitful results in order to improve a bench-to-bedside approach to translational research. On the basis of theoretical and experimental results obtained so far are we or not at the point: from bench to bedside and back again? As you will see, the answers to this question are complex, but one thing is clear: Translation into clinics is a tortuous and difficult path. Here, we provide a critical review about the available multifunctional gold nanocarriers for in vitro application and in vivo cancer targeting on nanodiagnostics and therapy.

The Next Generation of Smart Gold Nanobeacons: Nanotheranostics is Ready for Prime Time

“…Such material platforms provide for the simultaneous detection of several gene-associated conditions and nanodevices with the ability to monitor real-time drug action [4]. As cancer is a dynamic and multifactorial disease that is heterogeneous in nature, it can greatly benefit from a treatment that provides diagnosis and is titrated to disease type and state.…”

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

“…Nevertheless, numerous disease target sites, such as liver and spleen, require systemic administration of siRNAs into the circulatory system and circulation throughout the vasculature prior to specific tissue accumulation [151]. For 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 35 specific applications that require targeted systemic delivery, nanocarriers may be functionalized with cell-specific ligands that allow receptor-mediated uptake into target cells, such as tumour cells.…”

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 REVIEW NANO TODAY 6 Despite the enormous efforts to develop NP based siRNA carriers, most of the studies have been performed in cell cultures, using reporter genes such as the green fluorescent protein or luciferase, allowing easy recording of the RNAi efficacy. Less abundant are studies employing pre-clinical animal models (mainly mouse) [18,28,31], or targeting biologically relevant genes, and very rare those reporting on clinical trials using inorganic nanoparticles [30,35]. In fact, there are no active clinical trials reporting the use of inorganic NPs to target any gene using siRNA delivery (see Table 2).…”

“…As such, in vivo evaluation of functional NPs using model organisms must be a priority to allow fast, cost and time saving screenings of intermediate and final abducts, before clinical trials are initiated [35]. Table 3.…”

Cancer Nanotheranostics: What Have We Learned so Far?

“…Nanomaterials-based delivery systems in Theranostics (Diagnostics & Therapy) provide better penetration of therapeutic and diagnostic substances within the body at a reduced risk in comparison to conventional therapies. At the present time, there is a growing need to enhance the capability of theranostics procedures where innovative multifunctional nanocarriers for cancer theranostics may allow the development of diagnostics systems such as colorimetric and immunoassays, and in therapy approaches through gene therapy, drug delivery and tumor targeting systems in cancer [3].…”