Small

This issue's cover highlights the fields of nanofabrication and bio-nanotechnology, two areas where Chad Mirkin has made substantial contributions. The main image of the cover combines these two themes, depicting the capture of DNA-functionalized nanoparticles by a nanoelectrode. This image from the Mirkin group appeared in the first issue of Small (Volume 1, Issue 1 published in 2005), providing a fitting introduction to this issue commemorating the first 20 years of Chad's career.

The cover image shows 500 nm scaled dielectric cubes with precise metal patterns (50 nm line width) including functional optical elements such as split-ring resonators (SRRs) on all faces. The cubes fold up spontaneously during the plasma etching of electron-beampatterned panels. This self-folding enables origami-inspired approaches to be extended to the nanoscale, allowing precisely patterned 3D structures to be self-assembled from flat (2D) panels in a parallel manner. Compared to planar patterns, arrangements of optically active elements in polyhedral geometries can augment functionality for optics and biosensing. For more information, please read the Communication “Nanoscale Origami for 3D Optics” by D. H. Gracias and co-workers, beginning on page 1943.

Rapid and accurate molecular blood analysis is essential for disease dia­gnosis and management. Field-effect transistor (FET) biosensors promise to advance blood point-of-care testing by offering desirable characteristics such as portability, high sensitivity, brief detection time, low manufacturing cost, multi­plexing, and label-free detection. By controlling device parameters, desirable FET biosensor performance and stability are obtained.

Graphene-based materials may find applications in a variety of fields. Following a general introduction to graphene and its derivatives, the synthesis, characterization, properties, and applications of graphene-based materials are discussed.

Functionalized nanoparticles provide a versatile platform for surface recognition of bio-macromolecules. This review highlights current advances in the tuning of nanoparticle monolayers for interaction with biomolecules and cells. The use of these engineered materials for delivery, hybrid nanomaterials, and biosensing applications is discussed.

Nanomedicine is an emerging field that applies concepts in nanotechnology to the development of novel diagnostics and therapeutics. Physical and chemical properties of particles, including size, shape, modulus, surface charge, and surface chemistry, play important roles in the efficacy of nanomedicines. This review focuses on the effect of particle physical and chemical properties on their interactions with cells in vitro and their pharmacokinetics and biodistribution in vivo.

The use of gold nanoparticles for intracellular delivery of siRNA has built up momentum over the last five years. The different strategies employed are described in detail. These strategies involve either direct conjugation of siRNA to the gold surface via a thiol/gold bond, or association via an electrostatic interaction.

The frontispiece image shows hollow spherical assemblies of nanoparticles arising from mixtures of metal salts, simple buffers, and carefully designed peptides. The structures are prepared in aqueous conditions at neutral pH. Importantly, small modifications of the peptide sequence leads to dramatic differences in the diameter of the nanoparticle superstructures, allowing one to construct either sub-50-nm hollow spherical structures or larger (>100 nm) hollow spherical structures. For more information, please read the Communication “Size-Controlled Peptide-Directed Synthesis of Hollow Spherical Gold Nanoparticle Superstructures” by N. L. Rosi and co-workers, beginning on page 1938.

Choose your favorite size: Peptide conjugates, BP–A_x–PEP_Au, direct the synthesis and assembly of gold nanoparticles into well-defined hollow spherical gold nanoparticle superstructures. The diameter of the superstructures can be dialed-in by choosing the proper number of alanine residues, x: x = 2 leads to superstructures with diameters larger than 100 nm while x = 3 leads to superstructures with sub-50-nm diameters.

Nanoscale self-folding of electron-beam lithography patterned templates is used to create 3D devices for optics and biosensing.

Afacile strategy for preparing 1D conducting polymer nanobelts with the width of the belts down to less than 50 nm is presented. Strong enhancement in the conductivity of individual polypyrrole (PPy) nanobelts is observed, due to lengthening of the π-conjugation length of PPy belts with decreasing belt width, as confirmed by micro-Raman measurements.

The formation and properties of glyco-DNA–gold nanoparticles (NP) with a multivalent presentation of DNA-glyco ligands is presented. These particles are equipped with two reversible binding modes, which enable reversible dissociation by two independent external stimuli: temperature-induced DNA duplex melting and displacement of the DNA-glyco ligands from the carbohydrate recognition domains with free sugar.

The design of nanoparticle-based receptors has generally focused on the design of ligand molecules for the particles' ligand shell. This study focuses on the development of supramolecular nanoparticle receptors through the mixing of two types of ligand molecules. The nanoparticle receptor is achieved via the self-assembly of two ligands that together create binding sites, whereas each of the two homoligand particles has no appreciable binding capability.

Trinuclear ruthenium clusters attached to Au nanoparticles can be partially reduced to form mixed-valence nanoclusters. The nanoparticles are synthesized using a modified Brust method. IR-SEC shows dynamic coalescence of the stretching vibrations of the carbonyls, ν(CO), indicating the electron transfer between Ru clusters attached via a π-conjugated bridge to NPs occurs on the picosecond timescale. Simulation of IR spectra gives k_et on the order of 10¹¹ s⁻¹.

Rare-earth upconversion nanobarcodes (UPNBs) have been developed for multi­plexed signaling. There is no optical cross talk between the upconversion optical code and any reporter dyes. The midrange IR radiation used to excite the upconversion materials does not excite dyes that absorb in the visible and UV region and, conversely, the upconversion materials are not excited by the visible lasers used to excite the organic dyes.

Fluorine-19-DNA-functionalized gold nanoparticles (¹⁹F-DNA AuNPs) are demonstrated to provide a ¹⁹F-NMR off–on switch in response to target-specific DNA hybridization events. AuNP-bound ¹⁹F-DNA produces a low intensity signal that is undetectable above background. Upon complementary DNA hybridization and subsequent¹⁹F-DNA release, the ¹⁹F-NMR signal becomes detectable. This method has the potential to be used both in vitro and in vivo to non-invasively detect and image specific nucleic acid binding events of interest.

Uptake of PEGylated gold nanoparticles by HeLa cells in the presence of acrylate is described. Nanoparticles that are usually not taken up readily cross the plasma membrane into the cytosol in the presence of acrylate. In addition, a method is described that allows the introduction of large amounts of pre-aggregated gold nanoparticles into the cells without compromising the cell viability.

Rapid colorimetric detection of magnesium ions is demonstrated via a convenient approach, based on EcoRI-modified gold nanoparticles and a specifically designed DNA duplex. EcoRI is an enzyme obtained from certain strains of Escherichia coli.

Actuatable gold nanoparticle dimers for protein sensing are presented. By monitoring the spectral blue shift in the hybridized bonding plasmon mode instead of the conventional refractive index changes on a single nanoparticle, dimers are shown to be able to detect target protein even in the presence of high levels of nonspecific binding in complex media such as serum.

Morphology-dependent drug loading capacities and release kinetics are observed from pH-responsive diblock copolymer-based nano-objects, derived from the same block copolymer precursor. Shell-crosslinked, rod-shaped nanostructures exhibit a higher doxorubicin-loading capacity and rate of release than do their spherical counterparts. The extent of crosslinking and the type of crosslinker is also demonstrated to affect the rate of release.

Chiral metallic nanohelices with periodicity in the submicrometer regime are made from twisted CdTe nanoribbons. These helices are highly effective in polarization rotation at wavelengths centered at their pitch length. Interestingly, the chiro-optical performance of helical nanoparticle assemblies is better than that of solid gold nanowires with similar geometries, which sets an important target for the design of metamaterials.

A facile methodology for the immobilization of polymersomes is demo­nstrated using ad-hoc synthesized, biotinylated copolymers or commercially available biotinylated phospholipids on streptavidin-decorated substrates. This allows the imaging of polymersomes using high-resolution techniques such as stimulated emission depletion microscopy and atomic force microscopy. This latter allows the gathering of other important functional parameters such as mechanical properties and surface topology, enabling characterization of these water-borne nanoparticles in wet conditions and hence in their natural environment.

Light sensitive, semisynthetic ion channels allow for the modulation of multi­ple channel properties. Covalent attachment of a photoswitchable spiropyran group to the entrance of a gramicidin A ion channel enables reversible control of both conductance and channel lifetime, which show opposite trends in behavior at high and low salt concentrations.

Multicomponent DNA-templated nanoparticle chains with controllable dimension and composition are fabricated by joining nanoparticle (NP)-coated DNA fragments with asymmetric sticky overhangs in a specific pattern. Nuclear magnetic resonance spectroscopy is used to investigate the proton relaxation properties for two- segmented multicomponent structures. The position, composition, and the pattern of the NP chains has an influence on proton relaxation.

A library of 120 nanoparticle conjugates is produced by simple one-pot thiol exchange reactions. The antibiotic activity of the conjugates toward Staphylococcus aureus is found to depend upon the combination of thiols assembled on the nanoparticles.

Small structural changes in the shape of nanostructures have profound effects on their optical properties. As the tip of Au nanopyramidal shells is removed, the complex plasmon modes shifted to lower wavelengths.

Based on a combination of colloidal self-assembly and atomic layer deposition, a facile approach is developed to create novel, high-quality, ordered cage structures of anatase TiO₂ with shape and morphology control using Ag nanocrystals of different shapes as templates.

Morphology-dependent templates for crystalline Au nanowire synthesis are prepared from programmable DNA–block-copolymer micelles, in which DNA serves as the polar head group of amphiphilic polymers. Intriguingly, successful templation depends on the morphology of the micelles, with nanowire formation only observed in the case where the soft template is in the ordered cylindrical phase.

The design and dual-mode locomotion of a parallel hybrid nanowire motor, powered by two sources–chemical and magnetic–are described. The hybrid nanomotor relies on a multisegment nanowire, with different portions responsible for catalytic and magnetic propulsion. Such hybrid nanomotors hold promise for the design of self-regulated nanovehicles that adapt their operation according to unexpected events.

Highly stable and tumor-specific SPECT/CT imaging nanoparticle probes are described. Cyclic RGD-PEGlyated gold nanoparticle probes with directly conjugated iodine-125 can specifically target α_vβ₃ integrin-expressing tumor cells and can be taken up by tumor cells via integrin α_vβ₃-receptor-mediated endocytosis with almost no cytotoxicity. The probes can target tumor sites in vivo only 10 min after intravenous injection. These probes can be excreted after tumor targeting.

Porous silicon-based microparticles are used to load cisplatin, an anti-cancer drug, using reductive chemistry that caps the drug into the pores by partially converting cisplatin into metallic platinum. Cellular toxicity with ovarian cancer cells demonstrates an enhanced toxic effect in comparison to free drugs.

The remarkable effect of end groups on the self-assembly of RAFT hydrophilic homopolymers is explored. These hydrophobically end-functionalized homopolymers assemble in solution to afford well-defined aggregates, which are characterized by dynamic and static light scattering and transmission electron microscopy.

The amount of lipid ink transferred during dip-pen lithography (DPN) is determined by measuring the harmonic oscillation of the microcantilever used for lithography before and after the writing process. From the measured frequency shift, picogram mass sensitivity is obtained for the determination of transferred lipid mass.

The facile anodic deposition of colloidal iridium oxide (IrO_x·nH₂O) thin films from [Ir(OH)₆]²⁻ solutions is described. The stable IrO_x·nH₂O nanoparticle films exhibit the lowest-reported overpotential, 0.20 V at 1.5 mA cm⁻² current density, for the oxygen evolution reaction (OER) and have an exchange current density for the OER of 4–8 × 10⁻¹⁰ A cm ⁻² at a 4 mC cm⁻² coverage of electroactive Ir.

Intracellular delivery using needles: Needle-shaped particles made from a biodegradable polymer, PLGA, are shown to deliver siRNA into cells with minimal toxicity. The particles lead to higher intracellular delivery compared to spheres by direct penetration into the cell membrane resulting in higher gene knockdown. The particles are engineered to switch to spherical shape on demand mitigating the toxicity due to continuous permeabilization.

The coexistance of permanently “dark” and emitting quantum dots (QD) is established using the correlation between the enhancement in the QD photoemission yield that occurs when self-assembled with polyhistidine-appended proteins and the fraction of individual “bright” QDs in a macroscopic sample.

A layer-by-layer capsule system subcompartmentalized with pH-responsive polymersomes loaded with Cy5-labeled plasmid DNA is formed for use as a novel drug-delivery carrier for the controlled release of DNA. The DNA is released from the capsules in response to pH changes between physiological and endocytic conditions.