A protein-stabilized multifunctional theranostic nanoplatform, gadolinium oxide-gold nanoclusters hybrid (GdO-AuNCs), is constructed for multimodal imaging and drug delivery. The GdO-AuNCs nanohybrid is developed by integrating GdO nanocrystals and gold nanoclusters into bovine serum albumin scaffold as a stabilizer. The nanohybrid exhibits favorable biocompatibility and is capable of enhancing the contrast in magnetic resonance and X-ray computed tomography imaging. Meanwhile, the integrated AuNCs component not only endows the nanohybrid to produce red fluorescence, but also sensitizes the generation of singlet oxygen (O) upon near-infrared laser stimulation at 808 nm. Bovine serum albumin surrounding the nanoparticles makes GdO-AuNCs a brilliant carrier for the delivery of indocyanine green (ICG). ICG loading endows the GdO-AuNCs-ICG nanocomposite with a near-infrared fluorescence imaging capability, and improves its photodynamic property and photothermal capability. Ultimately, further experiments have demonstrated that GdO-AuNCs-ICG nanocomposite is a promising theranostic agent for image guided cancer therapy.

Nitrogen-doped carbon dots exhibit a distinct pH-sensitive/excitation-dependent photoluminescence emission feature within pH 4.0–8.0, facilitating intracellular pH sensing and multicolor imaging of live HeLa cells.

Tunable fluorescent emission and applications in both in vitro and in vivo imaging of hydrophobic carbon nanodots (CNDs) with rapid penetration capability are reported. The hydrophobic CNDs are prepared via hydrothermal treatment of ionic liquid 1-ethyl-3-methylimidazolium bromide and exhibit excitation-dependent photoluminescence behavior along with a red-shift in the excitation/emission maxima with concentration. The quantum yields of the as-prepared CNDs are in the range of 2.5-4.8% at an excitation wavelength of 300-600 nm. The rapid penetration behavior (within 1 min) of CNDs into the cell membrane significantly reduces the sample treatment time and avoids potential fluorescence quenching induced by the interaction between CNDs and samples. A co-location study reveals that the hydrophobic CNDs are distributed mainly in the lysosome. The potentials of the hydrophobic CNDs as fluorescent probe in in vitro and in vivo imaging are well demonstrated by the labeling of HeLa cells, MCF-7 cells, A549 cells, and Kunming mice.

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Water-soluble and functional copper nanoclusters (CuNCs) were prepared by using folic acid (FA) that serves both as a reducing reagent and a stabilizer. FA also acts as a functional ligand on the surface of the CuNCs, and this can be exploited to target the folate receptor which is over-expressed on the surface of HeLa cells. The FA-modified CuNCs nanoclusters have an average size of ca. 0.9 nm and are stable in aqueous medium for 30 days. Under photoexcitation at λ 270 and 350 nm, the FA-CuNCs display strong blue fluorescence with an emission peak at 440 nm. The FA-CuNCs exhibit low cytotoxicity and favorable biocompatibility as demonstrated by an MTT assay. A cell viability of>80% is found when incubating HeLa cells for 20 h with FA-CuNCs at levels of up to 200 μg mL. The targeting capability of the FA-CuNCs is demonstrated by live cell imaging. It is shown that HeLa cells with over-expressed folate receptor are much brighter than A549 cells where the receptor is not over-expressed. This is further corroborated by the fact that the copper content in HeLa cells (1.5 pg/cell) is 6.5-fold higher than that of A549 cells (0.23 pg/cell), both measured after the same incubation time of 3 h. If free FA is introduced into the cell culture medium, the folate receptors will be preoccupied with FA, and this results in a significant decrease in the cellular uptake of the FA-CuNCs by HeLa cells. Graphical Abstract Biocompatible copper nanoclusters (CuNCs) coated with folic acid (FA) were prepared and are shown to be viable probes for the differentiation between FR-positive HeLa cells and FR-negative A549 cells.