Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanisms and their miRNA complement are poorly characterized. Here we microRNA (miRNA)-profiled MSC exosomes and conducted a network analysis to identify the dominant biological processes and pathways modulated by exosomal miRNAs. At a system level, miRNA-targeted genes were enriched for (cardio)vascular and angiogenesis processes in line with observed cardiovascular regenerative effects. Targeted pathways were related to Wnt signaling, pro-fibrotic signaling via TGF-β and PDGF, proliferation, and apoptosis. When tested, MSC exosomes reduced collagen production by cardiac fibroblasts, protected cardiomyocytes from apoptosis, and increased angiogenesis in HUVECs. The intrinsic beneficial effects were further improved by virus-free enrichment of MSC exosomes with network-informed regenerative miRNAs capable of promoting angiogenesis and cardiomyocyte proliferation. The data presented here help define the miRNA landscape of MSC exosomes, establish their biological functions through network analyses at a system level, and provide a platform for modulating the overall phenotypic effects of exosomes.

Plasmonic copper sulfide-based colloidal nanocrystals (NCs) have attracted considerable attention due to their unique and versatile optical and electronic properties. In this Feature Article, we first introduce the optical properties of these p-type semiconductor nanostructures, particularly localized surface plasmon resonance (LSPR). We then discuss nanostructures of copper sulfides [CuS and Cu 2−x S, (0 ≤ x < 1)] with different crystal structures and optical properties. In addition to the synthesis and transformation between these copper sulfide phases, we review their doping or alloying with extrinsic cations, which can produce homogeneous alloy nanostructures, new crystal phases, and multidomain (e.g., core−shell or dimer) NCs. In general, divalent cations (e.g., Zn, Hg, Cd) do not form a homogeneous phase upon incorporation into copper sulfide NCs, but trivalent and tetravalent cations (e.g., In, Sn, Ga) can do so. Filling of the Cu vacancies responsible for p-type doping results in red-shifting and damping of the LSPR upon incorporation of extrinsic elements. Finally, we present some emerging applications of copper sulfide-based nanomaterials.

We report a new type of heterogeneous nanoparticles (NPs) composed of a heavily doped semiconductor domain (Cu2-xSe) and a metal domain (Au), which exhibit a broad localized surface plasmon resonance (LSPR) across visible and near-infrared (NIR) wavelengths, arising from interactions between the two nanocrystal domains. We demonstrate both in vivo photoacoustic imaging and in vitro dark field imaging, using the broad LSPR in Cu2-xSe-Au hybrid NPs to achieve contrast at different wavelengths. The high photoacoustic imaging depth achieved, up to 17 mm, shows that these novel contrast agents could be clinically relevant. More broadly, this work demonstrates a new strategy for tuning LSPR absorbance by engineering the density of free charge carriers in two interacting domains.

Preparation of nanomaterials with controllable size and shape at ambient conditions, without heating or cooling, is extremely attractive from the perspective of cost and energy efficiency. However, highly reactive precursors must be used to obtain NCs at ambient conditions, and this can make the control of particle formation extremely challenging. Degenerately p-doped copper sulfide NCs have attracted much recent interest based on the observation of localized surface plasmon resonance (LSPR) in these materials. These earth-abundant semiconductor NCs have potential applications ranging from photovoltaics to biomedical imaging. Here, we provide the first report of ambient-temperature preparation of covellite nanoplatelets. The lateral dimensions of these are controllable over a wide range while maintaining a constant thickness of 4 nm. The crystalline phase of the NCs is shown here to be controlled by the oxidation state of copper reagent, with a Cu(II) precursor required to prepare phase-pure covellite NCs. The NCs exhibit LSPR absorbance that depends upon their aspect ratio (their lateral dimension, at fixed thickness) and can be tuned over a range of more than 600 nm. Their optical absorbance was modelled quantitatively to extract consistent values of free carrier concentration and background polarizability that apply over a wide range of NC sizes.

Copper deficient copper sulfides (Cu2–x S, 0 ≤ x ≤ 1) are earth abundant, nontoxic materials with size-, phase-, and composition-dependent localized surface plasmon resonance (LSPR). Although synthesis of Cu2–x S nanocrystals (NCs) has attracted substantial research attention, understanding of the transformations of copper sulfides between their many possible stoichiometries and crystal phases is still lacking. Here, we develop a reversible transformation between CuS, which has a high density of free charge carriers and strong LSPR, and high chalcocite Cu2S with no LSPR. Initial CuS nanoplatelets (NPls) with a diameter of 55 nm and thickness of 4 nm were transformed into round high chalcocite Cu2S NPls with a diameter of 29.2 ± 2.0 nm and a thickness of 10.8 ± 0.7 nm by treatment with 1-dodecanethiol (DDT), which can reduce disulfide bonds in covellite. Treatment with an oleic acid–sulfur complex (OA-S), which serves as a sulfur source, can restore the hexagonal shape of the original CuS NPls during the reverse transformation from Cu2S to CuS, producing hexagonal NPls with a diameter of 43.1 ± 2.0 nm and thickness of 11.2 ± 0.9 nm. We also treated monodisperse, spherical roxbyite (Cu1.78S) NCs with OA-S and obtained hexagonal CuS NPls, showing that the tendency of CuS to form hexagonal NPls is an intrinsic result of its crystal structure. For comparison, we used different sulfur precursors to drive the transformation from Cu2S to CuS, illustrating the different reactivities of S-sources with Cu2S. This interconversion not only provides a better understanding of possible transformations in copper sulfide nanostructures but also provides new possibilities for the well-controlled colloidal synthesis of these nanomaterials with combinations of phase, size, shape, and LSPR energy not previously obtainable.