Using gold nanoparticles to detect single-nucleotide polymorphisms: toward liquid biopsy.

The possibility of detecting genetic mutations rapidly in physiological media through liquid biopsy has attracted the attention within the materials science community. The physical properties of nanoparticles combined with robust transduction methods ensure an improved sensitivity and specificity of a given assay and its implementation into point-of-care devices for common use. Covering the last twenty years, this review gives an overview of the state-of-the-art of the research on the use of gold nanoparticles in the development of colorimetric biosensors for the detection of single-nucleotide polymorphism as cancer biomarker. We discuss the main mechanisms of the assays that either are assisted by DNA-based molecular machines or by enzymatic reactions, summarize their performance and provide an outlook towards future developments.

Nanoparticle-Based Discrimination of Single-Nucleotide Polymorphism in Long DNA Sequences.

Circulating DNA (ctDNA) and specifically the detection cancer-associated mutations in liquid biopsies promises to revolutionize cancer detection. The main difficulty however is that the length of typical ctDNA fragments (∼150 bases) can form secondary structures potentially obscuring the mutated fragment from detection. We show that an assay based on gold nanoparticles (65 nm) stabilized with DNA (Au@DNA) can discriminate single nucleotide polymorphism in clinically relevant ssDNA sequences (70-140 bases). The preincubation step was crucial to this process, allowing sequential bridging of Au@DNA, so that single base mutation can be discriminated, down to 100 pM concentration.

Cancer Cell Internalization of Gold Nanostars Impacts Their Photothermal Efficiency In Vitro and In Vivo: Toward a Plasmonic Thermal Fingerprint in Tumoral Environment.

Gold nanoparticles are prime candidates for cancer thermotherapy. However, while the ultimate target for nanoparticle-mediated photothermal therapy is the cancer cell, heating performance has not previously been evaluated in the tumoral environment. A systematic investigation of gold nanostar heat-generating efficiency in situ is presented: not only in cancer cells in vitro but also after intratumoral injection in vivo. It is demonstrated that (i) in aqueous dispersion, heat generation is governed by particle size and exciting laser wavelength; (ii) in cancer cells in vitro, heat generation is still very efficient, but irrespective of both particle size and laser wavelength; and (iii) heat generation by nanostars injected into tumors in vivo evolves with time, as the nanostars are trafficked from the extracellular matrix into endosomes. The plasmonic heating response thus serves as a signature of nanoparticle internalization in cells, bringing the ultimate goal of nanoparticle-mediated photothermal therapy a step closer.

Antibonding plasmon modes in colloidal gold nanorod clusters.

The optical response of nanoplasmonic colloids in disperse phase is strictly related to their shape. However, upon self-assembly, new optical features, for example, bonding or antibonding modes, emerge as a result of the mutual orientations of nanoparticles. The geometry of the final assemblies often determines which mode is dominating in the overall optical response. These new plasmon modes, however, are mostly observed in silico, as self-assembly in the liquid phase leads to cluster formation with a broad range of particle units. Here we show that low-symmetry clustering of gold nanorods (AuNRs) in solution can also reveal antibonding modes. We found that UV-light irradiation of colloidal dispersions of AuNRs in N-methyl-2-pyrrolidone (NMP), stabilized by poly(vinylpyrrolidone) (PVP) results in the creation of AuNRs clusters with ladderlike morphology, where antibonding modes can be identified. We propose that UV irradiation induces formation of radicals in solvent molecules, which then promote cross-linking of PVP chains on the surface of adjacent particles. This picture opens up a number of relevant questions in nanoscience and is expected to find application in light induced self-assembly of particles with various compositions and morphologies.