Color is everything: Hg2+ in aqueous media is detected by the formation of thymidine–Hg2+–thymidine coordination complexes, which raises the melting temperature of the DNA‐hybridized gold nanoparticle probes and thus the temperature at which the probes disperse and effect a purple‐to‐red color change. The method has very high sensitivity and selectivity, and it provides a simple and fast colorimetric readout (see picture).

We report a new strategy for preparing silver nanoparticle-oligonucleotide conjugates that are based upon DNA with cyclic disulfide-anchoring groups. These particles are extremely stable and can withstand NaCl concentrations up to 1.0 M. When silver nanoparticles functionalized with complementary sequences are combined, they assemble to form DNA-linked nanoparticle networks. This assembly process is reversible with heating and is associated with a red shifting of the particle surface plasmon resonance and a concomitant color change from yellow to pale red. Analogous to the oligonucleotide-functionalized gold nanoparticles, these particles also exhibit highly cooperative binding properties with extremely sharp melting transitions. This work is an important step toward using silver nanoparticle-oligonucleotide conjugates for a variety of purposes, including molecular diagnostic labels, synthons in programmable materials synthesis approaches, and functional components for nanoelectronic and plasmonic devices.

We report the development of a highly sensitive and selective colorimetric detection method for cysteine based upon oligonucleotide-functionalized gold nanoparticle probes that contain strategically placed thymidine-thymidine (T-T) mismatches complexed with Hg2+. This assay relies upon the distance-dependent optical properties of gold nanoparticles, the sharp melting transition of oligonucleotide-linked nanoparticle aggregates, and the very selective coordination of Hg2+ with cysteine. The concentration of cysteine can be determined by monitoring with the naked eye or a UV-vis spectrometer the temperature at which the purple-to-red color change associated with aggregate dissociation takes place. This assay does not utilize organic cosolvents, enzymatic reactions, light-sensitive dye molecules, lengthy protocols, or sophisticated instrumentation thereby overcoming some of the limitations of more conventional methods.

We have developed the chemistry for preparing a universal probe and the appropriate nano- and microparticle labels that can be used to do highly selective multiplexed detection of three protein cancer markers at low-femtomolar concentration in buffer and serum media. The approach relies on a new multiplexed version of the biobarcode amplification method and offers new opportunities for studying multiple protein markers in a single sample. This could lead to new forms of disease diagnosis and monitoring disease recurrence in a variety of settings.

The safe and effective delivery of RNA therapeutics remains the major barrier to their broad clinical application. Here we develop a new nanoparticulate delivery system based on inorganic particles and biodegradable polycations. First, gold nanoparticles were modified with the hydrophilic polymer poly(ethylene glycol) (PEG), and then small interfering RNA (siRNA) was conjugated to the nanoparticles via biodegradable disulfide linkages, with ~30 strands of siRNA per nanoparticle. The particles were then coated with a library of end-modified poly(β-amino ester)s (PBAEs), previously identified as capable of facilitating intracellular DNA delivery. Nanoparticulate formulations developed here facilitate high levels of in vitro siRNA delivery, facilitating delivery as good or better than the commercially available lipid reagent, Lipofectamine 2000.RNA interference (RNAi) is an endogenous process whereby double-stranded RNA (dsRNA) can mediate the catalytic destruction of its homologous mRNA target. Short 22 nt dsRNA fragments called small interfering RNA (siRNA), are intermediates in the process and have shown their potential as therapeutics. 1-4 The development of RNAi based upon synthetic siRNA has led to a variety of potential therapeutic applications for diseases whose conventional treatments are limited. 5-9 The safe and effective intracellular delivery of siRNA remains the most challenging barrier to the broad application of siRNA in the clinic. [10][11][12][13][14] To date a number of carriers have been investigated for their potential as siRNA delivery agents 15 including cationic polymers, 16,17 lipids 8 or lipid-like materials, 18 iron oxide nanoparticles, 19 gold particles, 20-22 and semiconductor nanocrystals. 23,24 Alternatively, siRNA has been chemically modified and conjugated to small organic molecules 25,26 or polymeric materials 12,27,28 to enhance its stability and cellular uptake. 15 Poly(β-amino ester)s (PBAEs) have shown potential as delivery agents for DNA in various cell lines and therapeutic models. [29][30][31][32][33][34][35][36] To the best of our knowledge, however, these materials have not yet demonstrated their ability to deliver siRNA. The disorderly interactions of siRNA with polymer are likely to result in incomplete condensation of the polymer into a particulate due to the stiffer nature of an RNA molecule relative to DNA ( Figure 1A). 37 We hypothesized