Fluorescence targeted imaging in vivo has proven useful in tumor recognition and drug delivery. In the process of in vivo imaging, however, a high autofluorescence background could mask the signals from the fluorescent probes. Herein, a high contrast upconversion luminescence (UCL) imaging protocol was developed for targeted imaging of tumors based on RGD-labeled upconversion nanophosphors (UCNPs) as luminescent labels. Confocal Z-scan imaging of tissue slices revealed that UCL imaging showed no autofluorescence signal even at high penetration depth (approximately 600 microm). More importantly, region of interest (ROI) analysis of the UCL signal in vivo showed that UCL imaging achieved a high signal-to-noise ratio (approximately 24) between the tumor and the background. These results demonstrate that the UCL imaging technique appears particularly suited for applications in tracking and labeling components of complex biological systems.

Methylmercury (MeHg(+)) is a strong liposoluble ion, which can be accumulated in the organs of animals and can cause prenatal nervous system and visceral damage. Therefore, the efficient and sensitive monitoring of MeHg(+) in organisms is of great importance. Upconversion luminescence (UCL) detection based on rare-earth upconversion nanophosphors (UCNPs) as probes has been proved to exhibit a large anti-Stokes shift, no autofluorescence from biological samples, a remarkably deep penetration depth, and no photobleaching. In this study, a hydrophobic heptamethine cyanine dye (hCy7) modified by two long alkyl moieties and amphiphilic polymer (P-PEG)-modified nanophosphors (hCy7-UCNPs) was fabricated as a highly sensitive water-soluble probe for UCL monitoring and bioimaging of MeHg(+). Further application of hCy7-UCNPs for sensing MeHg(+) was confirmed by an optical titration experiment and upconversion luminescence live cell imaging. Using the ratiometric upconversion luminescence as a detection signal, which provides a built-in correction for environmental effects, the detection limit of MeHg(+) for this nanosystem was as low as 0.18 ppb. Importantly, the hCy7-UCNPs nanosystem was shown to be capable of monitoring MeHg(+)ex vivo and in vivo by upconversion luminescence bioimaging.

The mononuclear phagocyte system (MPS, e.g., liver and spleen) is often treated as a 'blackbox' by nano-researchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, we exploit this imperfection by applying nano-antioxidants with preferential liver uptake to directly prevent hepatic ischemia-reperfusion injury (IRI), which is a reactive oxygen species (ROS)related disease. Ceria nanoparticles (NPs) were selected as a representative nano-antioxidant and detailed mechanism of preventing IRI was investigated. We found that ceria NPs effectively alleviated the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro-inflammatory cytokines were then significantly reduced and the recruitment and infiltration of neutrophils were minimized, which suppressed subsequent inflammatory reaction involved in the liver. The protective effect of nanoantioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.

Uniform silica-coated NaYF(4): 20 mol % Yb, 2 mol % Er nanocomposites with good dispersibility, containing organic dye incorporated in the silica shell and folic acid conjugated on the surface of the shell, were prepared and characterized. The core-shell nanocomposites are 20-22 nm in size, water soluble, and buffer stable, with good photostability and biocompatibility. Folic acid (FA) offers a means of targeting human cells that greatly overexpress the folate receptor (FR). By the use of confocal microscopy and quantitative flow cytometry analysis, we demonstrate the receptor-mediated delivery of FA-conjugated nanocomposites targeting FR-positive cell lines, such as KB cells. The receptor-mediated targeting was confirmed by a comparison with the uptake of these nanocomposites in FR-negative cell lines, such as MCF-7. These results show that the silica-coated upconverting nanophosphor (UCNP) nanocomposites prepared by our strategy can potentially be useful as multimodal bioimaging agents.

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