Gold nanobeacon

Theranostics

Recently, Conde et al. developed a new theranostic system capable of intersecting all RNA pathways: from gene specific downregulation to silencing the silencers, i.e. siRNA and miRNA pathways. The authors reported the development of new nanomaterials, i.e. gold nanoparticles functionalized with a fluorophore labeled hairpin-DNA.

Bioresponsive antisense DNA gold nanobeacons for the inhibition of cancer cells and metastasis

Gold nanobeacons can be used as a tool for cancer theranostics. Recently, Conde et al. developed a nanomaterial platform based on gold nanobeacons to detect, target and inhibit the expression of a mutant Kras gene in an in vivo murine gastric cancer model. The conjugation of fluorescently-labeled antisense DNA hairpin oligonucleotides to the surface of gold nanoparticles enables using their localized surface plasmon resonance properties to directly track the delivery to the primary gastric tumor and to lung metastatic sites. The fluorescently labeled nanobeacons reports on the interaction with the target as the fluorescent Cy3 signal is quenched by the gold nanoparticle and only emit light following conjugation to the Kras target owing to reorganization and opening of the nanobeacons, thus increasing the distance between the dye and the quencher. The systemic administration of the anti-Kras nanobeacons resulted in approximately 60% tumor size reduction and a 90% reduction in tumor vascularization. More important, the inhibition of the Kras gene expression in gastric tumors prevents the occurrence of metastasis to lung (80% reduction), increasing mice survival in more than 85%. The developed platform can be easily adjusted to hybridize with any specific target and provide facile diagnosis and treatment for neoplastic diseases.

2-pair FRET/NSET nanoswitch to sense, inhibit and deliver drugs

Now with one single local application using hydrogel scaffolds embedded with a 2-pair FRET/NSET (Fluorescence Resonance Energy Transfer/NanoSurface Energy Transfer) gold nanobeacons (also known as dark-gold nanobeacons) we are able to overcome drug resistance by detecting and silencing a multidrug resistance protein (MRP1), before chemotherapeutic drug delivery in vivo. Our platform contains hydrogel embedded with dark-gold nanoparticles modified with 5-fluorouracil (5-FU)-intercalated nanobeacons that serve as an ON/OFF molecular nanoswitch triggered by the increased MRP1 expression within the tumour tissue microenvironment. This nanoswitch can sense and overcome multidrug resistance (MDR) prior to local drug release. These nanoprobes comprise a thiol-DNA-hairpin labelled with a NIR dye and a thiol-DNA oligo labelled with a dark quencher (BHQ2), polyethylene glycol (PEG), and intercalated drug- all of which are conjugated to a gold nanoparticle core. These dark-gold nanobeacons are then loaded with 5-FU that intercalates in the beacon stem (dsDNA part) of the DNA-hairpin oligo. Under hairpin configuration, the proximity of the NIR dye to the dark quencher leads to fluorescence quenching. Hybridization of the DNA hairpin to a complementary mRNA target restores fluorescence emission due to the gold nanobeacons' conformational reorganization that causes the fluorophore and the quencher to part from each other, yielding a quantitative response. On the other hand, the release of the 5-FU drug can only occur when DNA hairpin hybridizes with the complementary target and can be measured once the distance from the 5-FU and the gold core increases, escalating the drug emission. To evaluate the efficiency of the dark-gold nanobeacon probes in sensing and in overcoming MDR in vivo, an orthotopic breast cancer mouse model was developed by injecting 5-FU resistant MDAMB-231 cells to the mammary fat pad of female SCID hairless congenic mice. Efficacious and local delivery of the dark-gold nanobeacon probes is achieved by the implantation of a hydrogel disk on top of the triple-negative breast tumours using a polyamidoamine (PAMAM G5) dendrimer cross-linked with dextran aldehyde, which provides enhanced stability of the embedded nanoparticles. Despite the cross-resistance to 5-FU, more than 90% tumour reduction is achieved in vivo, following 80% MRP1 silencing compared with the continuous tumour growth following only drug or nonsense nanobeacon administration.