Colloidal nanoparticles are being intensely pursued in current nanoscience research. Nanochemists are often frustrated by the well-known fact that no two nanoparticles are the same, which precludes the deep understanding of many fundamental properties of colloidal nanoparticles in which the total structures (core plus surface) must be known. Therefore, controlling nanoparticles with atomic precision and solving their total structures have long been major dreams for nanochemists. Recently, these goals are partially fulfilled in the case of gold nanoparticles, at least in the ultrasmall size regime (1–3 nm in diameter, often called nanoclusters). This review summarizes the major progress in the field, including the principles that permit atomically precise synthesis, new types of atomic structures, and unique physical and chemical properties of atomically precise nanoparticles, as well as exciting opportunities for nanochemists to understand very fundamental science of colloidal nanoparticles (such as the s...

Atomically Precise Colloidal Metal Nanoclusters and Nanoparticles: Fundamentals and Opportunities

Ultra-small fluorescent metal nanoclusters: Synthesis and biological applications

Chemistries that Facilitate Nanotechnology Kim E. Sapsford,† W. Russ Algar, Lorenzo Berti, Kelly Boeneman Gemmill,‡ Brendan J. Casey,† Eunkeu Oh, Michael H. Stewart, and Igor L. Medintz*,‡ †Division of Biology, Department of Chemistry and Materials Science, Office of Science and Engineering Laboratories, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States ‡Center for Bio/Molecular Science and Engineering Code 6900 and Division of Optical Sciences Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, United States College of Science, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, California 95817, United States Sotera Defense Solutions, Crofton, Maryland 21114, United States

Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology.

Gold Nanomaterials at Work in Biomedicine

Metal nanoclusters: New fluorescent probes for sensors and bioimaging

The fluorescence of metal nanoclusters provides an amusing optic feature to be applied in various fields. However, rational design of dual functional fluorescent metal nanoclusters directed by active enzyme with targeted application remains little explored. In this work, we report a new strategy to construct enzyme functionalized fluorescent gold nanoclusters via a biomineralization process for the detection of hydrogen peroxide. Horseradish peroxidase (HRP) was used as a model functional template to direct the synthesis of fluorescent gold nanoclusters (Au NCs) at physiological conditions to form HRP−Au NCs bioconjugates. We found that the fluorescence of HRP−Au NCs can be quenched quantitatively by adding H2O2, indicating that HRP enzyme remains active and enables catalytic reaction of HRP−Au NCs and H2O2. Upon the addition of H2O2 under optimal conditions, the fluorescence intensity quenched linearly over the range of 100 nM to 100 μM with high sensitivity (LOD = 30 nM, S/N = 3). This study would be po...

Horseradish peroxidase functionalized fluorescent gold nanoclusters for hydrogen peroxide sensing.

We developed a colorimetric sensor array with reported protein aptamers as nonspecific receptors. We found that different target proteins could make the aptamer-protected gold nanoparticles (AuNPs) exhibit different aggregation behaviors in the presence of a high concentration salt and cause various color change. On the basis of this phenomenon, we applied a series of reported protein aptamers as a receptor array obtaining a distinct response pattern to each target protein. Seven proteins have been well distinguished with the naked eye at the 50 nM level. Cancerous human cells have also been discriminated from noncancerous cells. This method is simple, label-free, and sensitive. It will broaden the application filed of plasmonic nanoparticle-based sensors and give a new direction of developing sensitive array sensing systems.

Aptamer-based plasmonic sensor array for discrimination of proteins and cells with the naked eye.

We constructed a DNA tetrahedron based multicolor nanoprobe, which could simultaneously imaging of three tumor-related mRNAs in living cells through fluorescence restoration caused by competitive chain replacement reaction. The oligonucleotides used to construct the tetrahedron were extended by adding three 21-base recognition sequences modified with different fluorophores (FAM, Cy3, and Cy5) in the 5′ end. Three 11-base complementary sequences modified with quencher (BHQ1 for FAM and BHQ2 for Cy3 and Cy5) were hybridized with the recognition sequences to quench the fluorescence. In the presence of the specific mRNA targets, the recognition sequences hybridized with the targets to form longer duplexes and the fluorescence was restored. Compared with previously reported nanoprobes based on DNA tetrahedron, the multicolor nanoprobe can effectively avoid false positive results.

Simultaneous Imaging of Three Tumor-Related mRNAs in Living Cells with a DNA Tetrahedron-Based Multicolor Nanoprobe

The discrimination of the type of cancer cells remains challenging due to the subtle differences in their expression of membrane receptors. In this work, we developed a multicolor cell imaging method for distinguishing the type of cancer cells with fluorophore-tagged aptamers. We found that the interaction between aptamers and cancer cells was affected by both of the sequence of aptamers and the labeled dyes. As the co-ownership of biomarkers for different cancer cell lines, the fluorophore-tagged aptamers interacted with different cancer cell lines in different degree, resulting in a distinct color to discriminate the type of cancer cells at single cell level. Taking advantage of the cross-reactive ability of the fluorophore-tagged aptamers, we could not only distinguish the cancerous cells quickly from large quantities of noncancerous cells, but also identify the type of the cancerous cells. This work has potential application for cancer diagnostic and therapy in the future.

Multicolor imaging of cancer cells with fluorophore-tagged aptamers for single cell typing.

Sensitive detection of biomolecules in small-volume samples by mass spectrometry is, in many cases, challenging because of the use of buffers to maintain the biological activities of proteins and cells. Here, we report a highly effective desalting method for picoliter samples. It was based on the spontaneous separation of biomolecules from salts during crystallization of the salts. After desalting, the biomolecules were deposited in the tip of the quartz pipet because of the evaporation of the solvent. Subsequent detection of the separated biomolecules was achieved using solvent assisted electric field induced desorption/ionization (SAEFIDI) coupled with mass spectrometry. It allowed for direct desorption/ionization of the biomolecules in situ from the tip of the pipet. The organic component in the assistant solvent inhibited the desorption/ionization of salts, thus assured successful detection of biomolecules. Proteins and peptides down to 50 amol were successfully detected using our method even if there...

Song Wang

Papers

Horseradish peroxidase functionalized fluorescent gold nanoclusters for hydrogen peroxide sensing.

Aptamer-based plasmonic sensor array for discrimination of proteins and cells with the naked eye.

Simultaneous Imaging of Three Tumor-Related mRNAs in Living Cells with a DNA Tetrahedron-Based Multicolor Nanoprobe

Multicolor imaging of cancer cells with fluorophore-tagged aptamers for single cell typing.

Desalting by Crystallization: Detection of Attomole Biomolecules in Picoliter Buffers by Mass Spectrometry