Semiconductor quantum dots (QDs) are tiny light-emitting particles on the nanometer scale, and are emerging as a new class of fluorescent labels for biology and medicine. In comparison with organic dyes and fluorescent proteins, they have unique optical and electronic properties, with size-tunable light emission, superior signal brightness, resistance to photobleaching, and broad absorption spectra for simultaneous excitation of multiple fluorescence colors. QDs also provide a versatile nanoscale scaffold for designing multifunctional nanoparticles with both imaging and therapeutic functions. When linked with targeting ligands such as antibodies, peptides or small molecules, QDs can be used to target tumor biomarkers as well as tumor vasculatures with high affinity and specificity. Here we discuss the synthesis and development of state-of-the-art QD probes and their use for molecular and cellular imaging. We also examine key issues for in vivo imaging and therapy, such as nanoparticle biodistribution, pharmacokinetics, and toxicology.

Afterglow optical agents, which emit light long after cessation of excitation, hold promise for ultrasensitive in vivo imaging because they eliminate tissue autofluorescence. However, afterglow imaging has been limited by its reliance on inorganic nanoparticles with relatively low brightness and short-near-infrared (NIR) emission. Here we present semiconducting polymer nanoparticles (SPNs) <40 nm in diameter that store photon energy via chemical defects and emit long-NIR afterglow luminescence at 780 nm with a half-life of ∼6 min. In vivo, the afterglow intensity of SPNs is more than 100-fold brighter than that of inorganic afterglow agents, and the signal is detectable through the body of a live mouse. High-contrast lymph node and tumor imaging in living mice is demonstrated with a signal-to-background ratio up to 127-times higher than that obtained by NIR fluorescence imaging. Moreover, we developed an afterglow probe, activated only in the presence of biothiols, for early detection of drug-induced hepatotoxicity in living mice.

We have successfully fabricated an asymmetric supercapacitor with high energy and power densities using graphene hydrogel (GH) with 3D interconnected pores as the negative electrode and vertically aligned MnO(2) nanoplates on nickel foam (MnO(2)-NF) as the positive electrode in a neutral aqueous Na(2)SO(4) electrolyte. Because of the desirable porous structure, high specific capacitance and rate capability of GH and MnO(2)-NF, complementary potential window of the two electrodes, and the elimination of polymer binders and conducting additives, the asymmetric supercapacitor can be cycled reversibly in a wide potential window of 0-2.0 V and exhibits an energy density of 23.2 Wh kg(-1) with a power density of 1.0 kW kg(-1). Energy density of the asymmetric supercapacitor is significantly improved in comparison with those of symmetric supercapacitors based on GH (5.5 Wh kg(-1)) and MnO(2)-NF (6.7 Wh kg(-1)). Even at a high power density of 10.0 kW kg(-1), the asymmetric supercapacitor can deliver a high energy density of 14.9 Wh kg(-1). The asymmetric supercapacitor also presents stable cycling performance with 83.4% capacitance retention after 5000 cycles.

We present a one-step approach to polydopamine-modified graphene hydrogel, with dopamine serving as both reductant and surface functionalization agents. The synthetic method is based on the spontaneous polymerization of dopamine and the self-assembly of graphene nanosheets into porous hydrogel structures. Benefiting from the abundant functional groups of polydopamine and the high specific surface areas of graphene hydrogel with three-dimensional interconnected pores, the prepared material exhibits high adsorption capacities toward a wide spectrum of contaminants, including heavy metals, synthetic dyes, and aromatic pollutants. Importantly, the free-standing graphene hydrogel can be easily removed from water after adsorption process, and can be regenerated by altering the pH values of the solution for adsorbed heavy metals or using low-cost alcohols for synthetic dyes and aromatic molecules.

We report the development of cell-penetrating quantum dots (QDs) based on the use of multivalent and endosome-disrupting (endosomolytic) surface coatings. Hyperbranched copolymer ligands such as polyethylene glycol (PEG) grafted polyethylenimine (PEI-g-PEG) are found to encapsulate and solubilize luminescent quantum dots through direct ligand-exchange reactions. Because of the positive charges and a "proton sponge effect" associated with multivalent amine groups, this class of ligand-exchanged QDs is able to penetrate cell membranes and is also able to disrupt endosomal organelles in living cells. The grafted PEG segment is essential for reducing the cytotoxicity of PEI as well as for improving the overall nanoparticle stability and biocompatibility. In comparison with previous QDs encapsulated with amphiphilic polymers, the cell-penetrating QDs are smaller in size and are considerably more stable in acidic environments. Cellular uptake and imaging studies reveal that the number of PEG grafts per PEI molecule has a pronounced effect on the intracellular pathways of internalized QDs. In particular, QDs coated with PEI-g-PEG2 are rapidly internalized by endocytosis, and are initially stored in vesicles, followed by slow endosomal escape and release into the cytoplasm. These insights are important toward the design and development of nanoparticle agents for intracellular imaging and therapeutic applications.

We report the development of bioconjugated plasmonic vesicles assembled from SERS-encoded amphiphilic gold nanoparticles for cancer-targeted drug delivery. This new type of plasmonic assemblies with a hollow cavity can play multifunctional roles as delivery carriers for anticancer drugs and SERS-active plasmonic imaging probes to specifically label targeted cancer cells and monitor intracellular drug delivery. We have shown that the pH-responsive disassembly of the plasmonic vesicle, stimulated by the hydrophobic-to-hydrophilic transition of the hydrophobic brushes in acidic intracellular compartments, allows for triggered intracellular drug release. Because self-assembled plasmonic vesicles exhibit significantly different plasmonic properties and greatly enhanced SERS intensity in comparison with single gold nanoparticles due to strong interparticle plasmonic coupling, disassembly of the vesicles in endocytic compartments leads to dramatic changes in scattering properties and SERS signals, which can serve as independent feedback mechanisms to signal cargo release from the vesicles. The unique structural and optical properties of the plasmonic vesicle have made it a promising platform for targeted combination therapy and theranostic applications by taking advantage of recent advances in gold nanostructure based in vivo bioimaging and photothermal therapy and their loading capacity for both hydrophilic (nucleic acids and proteins) and hydrophobic (small molecules) therapeutic agents.

A number of procedures are currently available to encapsulate and solubilize hydrophobic semiconductor Quantum Dots (QDs) for biological applications. Most of these procedures are based on the use of small-molecule coordinating ligands, amphiphilic polymers, or amphiphilic lipids. However, it is still not clear how these different surface coating molecules affect the optical, colloidal, and chemical properties of the solubilized QDs. Here we report a systematic study to examine the effects of surface coating chemistry on the hydrodynamic size, fluorescence quantum yield, photostability, chemical stability, and biocompatibility of water-soluble QDs. The results indicate that quantum dots with the smallest hydrodynamic sizes are best prepared by direct ligand exchange with hydrophilic molecules, but the resulting particles are less stable than those encapsulated in amphiphilic polymers. For stability against chemical oxidation, QDs should be protected with a hydrophobic bilayer. For high stability under acidic conditions, the best QDs are prepared by using hyperbranched polyethylenimine. For stability in high salt buffers, it is preferable to have uncharged, sterically-stabilized QDs, like those coated with polyethylene glycol (PEG). These insights are expected to benefit the development of quantum dots and related nanoparticle probes for molecular and cellular imaging applications.

We report a novel ligand-induced etching process in which hyperbranched and multivalent coordinating polymers such as polyethylenimine (PEI) react with preformed gold nanocrystals to form atomic gold clusters that are soluble in water and are highly fluorescent upon UV light excitation. These “as-prepared” fluorescent clusters appear to be in an oxidized electronic state, with their excitation and emission maxima located at 421 and 505 nm, respectively. Upon treatment by strong reducing agents such as NaBH4, the cluster's excitation and emission peaks are shifted to 353 and 445 nm. Electrospray ionization (ESI) mass spectrometry data indicate that the light-emitting species are small atomic nanoclusters consisting of only 8 gold atoms (Au8). There is also evidence to suggest that a ligand-to-metal electronic transition in the ultraviolet is superimposed on the cluster absorption spectra, but it is not directly related to the intrinsic fluorescent properties of these atomic clusters. These surprising results suggest that ligand-induced etching could be used to prepare new types of fluorescent metal nanoclusters for applications in catalysis and biological labeling.