A CORM loaded nanoplatform for single NIR light-activated bioimaging, gas therapy, and photothermal therapy in vitro.

Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.

Laser-induced breakdown spectroscopy as a straightforward bioimaging tool for plant biologists; the case study for assessment of photon-upconversion nanoparticles in Brassica oleracea L. plant.

The main purpose of this work is to thoroughly describe the implementation protocol of laser-induced breakdown spectroscopy (LIBS) method in the plant analysis. Numerous feasibility studies and recent progress in instrumentation and trends in chemical analysis make LIBS an established method in plant bioimaging. In this work, we present an easy and straightforward phytotoxicity case study with a focus on LIBS method. We intend to demonstrate in detail how to manipulate with plants after exposures and how to prepare them for analyses. Moreover, we aim to achieve 2D maps of spatial element distribution with a good resolution without any loss of sensitivity. The benefits of rapid, low-cost bioimaging are highlighted. In this study, cabbage (Brassica oleracea L.) was treated with an aqueous dispersion of photon-upconversion nanoparticles (NaYF4 doped with Yb3+ and Tm3+ coated with carboxylated silica shell) in a hydroponic short-term toxicity test. After a 72-hour plant exposure, several macroscopic toxicity end-points were monitored. The translocation of Y, Yb, and Tm across the whole plant was set by employing LIBS with a lateral resolution 100 µm. The LIBS maps of rare-earth elements in B.oleracea plant grown with 50 µg/mL nanoparticle-treated and ion-treated exposures showed the root as the main storage, while the transfer via stem into leaves was minimal. On the contrary, the LIBS maps of plants exposed to the 500 µg/mL nanoparticle-treated and ion-treated uncover slightly different trends, nanoparticles as well as ions were transferred through the stem into leaves. However, the main storage organ was a root as well.

Reversible Ratiometric Probe Combined with the Time-Gated Method for Accurate In Vivo Gastrointestinal pH Sensing.

Fluorescence sensing has the advantages of being real time, noninvasive, and convenient and having a low impact on the original environment for in vivo detection. Here, a reversible time-gated ratiometric in vivo detection method that could eliminate the interferences from probe amount, photon scattering, and absorption is proposed. Correspondingly, the composite probe must be able to reversibly respond to changes in the microenvironment and emit two luminescence signals at the same working wavelength but different lifetimes. Benefitting from the reversible detection mechanism, the probes could be used to monitor a dynamic biological process and the ratio signal value could be determined only by the concentration of analytes, independent of the probe concentration. Furthermore, benefitting from the same working wavelength, the read-out errors from photon absorption and scattering could be minimized. This method is very suitable for in vivo detection in which the probe distribution and depth are unknown and variable. As a typical model, different pH values in the gastrointestinal area and pH changes caused by drugs and fasting are successfully monitored.

Optical Control of Metal Ion Probes in Cells and Zebrafish Using Highly Selective DNAzymes Conjugated to Upconversion Nanoparticles.

Spatial and temporal distributions of metal ions in vitro and in vivo are crucial in our understanding of the roles of metal ions in biological systems, and yet there is a very limited number of methods to probe metal ions with high space and time resolution, especially in vivo. To overcome this limitation, we report a Zn2+-specific near-infrared (NIR) DNAzyme nanoprobe for real-time metal ion tracking with spatiotemporal control in early embryos and larvae of zebrafish. By conjugating photocaged DNAzymes onto lanthanide-doped upconversion nanoparticles (UCNPs), we have achieved upconversion of a deep tissue penetrating NIR 980 nm light into 365 nm emission. The UV photon then efficiently photodecages a substrate strand containing a nitrobenzyl group at the 2'-OH of adenosine ribonucleotide, allowing enzymatic cleavage by a complementary DNA strand containing a Zn2+-selective DNAzyme. The product containing a visible FAM fluorophore that is initially quenched by BHQ1 and Dabcyl quenchers is released after cleavage, resulting in higher fluorescent signals. The DNAzyme-UCNP probe enables Zn2+ sensing by exciting in the NIR biological imaging window in both living cells and zebrafish embryos and detecting in the visible region. In this study, we introduce a platform that can be used to understand the Zn2+ distribution with spatiotemporal control, thereby giving insights into the dynamical Zn2+ ion distribution in intracellular and in vivo models.

Hydrothermal synthesis of NaLuF4:153Sm,Yb,Tm nanoparticles and their application in dual-modality upconversion luminescence and SPECT bioimaging.

Upconversion luminescence (UCL) properties and radioactivity have been integrated into NaLuF(4):(153)Sm,Yb,Tm nanoparticles by a facile one-step hydrothermal method, making these nanoparticles potential candidates for UCL and single-photon emission computed tomography (SPECT) dual-modal bioimaging in vivo. The introduction of small amount of radioactive (153)Sm(3+) can hardly vary the upconversion luminescence properties of the nanoparticles. The as-designed nanoparticles showed very low cytotoxicity, no obvious tissue damage in 7 days, and excellent in vitro and in vivo performances in dual-modal bioimaging. By means of a combination of UCL and SPECT imaging in vivo, the distribution of the nanoparticles in living animals has been studied, and the results indicated that these particles were mainly accumulated in the liver and spleen. Therefore, the concept of (153)Sm(3+)/Yb(3+)/Tm(3+) co-doped NaLuF(4) nanoparticles for UCL and SPECT dual-modality imaging in vivo of whole-body animals may serve as a platform for next-generation probes for ultra-sensitive molecular imaging from the cellular scale to whole-body evaluation. It also introduces an easy methodology to quantify in vivo biodistribution of nanomaterials which still needs further understanding as a community.

Bioimaging and toxicity assessments of near-infrared upconversion luminescent NaYF4:Yb,Tm nanocrystals.

In vitro or in vivo bioimaging utilizing the upconversion (UC) luminescence of rare earth fluoride nanocrystals (NCs) has attracted much attention, especially for Yb(3+)/Tm(3+) doped NCs with a near-infrared (NIR) UC emission at 800 nm. Herein, water-soluble NaYF(4):Yb,Tm NCs with strong NIR UC emission were synthesized with a solvothermal method. In vitro and in vivo bioimaging and toxicity assessments were carried out with HeLa cell and Caenorhabditis elegans (C. elegans) cases, respectively. NaYF(4):Yb,Tm NCs afforded an efficient NIR image of the HeLa cells with an incubation concentration of 10 µg mL(-1), and CCK-8 assay revealed a low cytotoxicity. Fed with Escherichia coli (E. coli) and NCs together, the C. elegans showed a NIR image in the gut from the pharynx to the anus. Further, these NCs could be excreted out when those worms were then fed with only E. coli. Toxicity studies were further addressed with protein expression, life span, egg production, egg viability, and growth rate of the worms in comparison with those of the intact ones. The feeding of rare earth fluoride NCs with a dose of 100 µg does not arise obvious toxicity effect from the growth to procreation. The in vitro and in vivo studies confirm that NaYF(4):Yb,Tm NCs could be served as an excellent NIR emission bioprobe with low toxicity.

Studies of nutritional safety of some heavy metals in mice.

Heavy metals have been proposed as nutrient markers to allow the accurate determination of the time of passage, nutrient intake, or apparent utilization of multiple nutrients. In order to evaluate possible toxic effects of scandium, chromium, lanthanum, samarium, europium, dysprosium, terbium, thulium, and ytterbium oxides, and barium sulfate upon growth, general development, reproduction, and lactation, mice were fed different levels of these compounds for three generations. The amount of elements fed were 0,110, 100, and 1000 times the use amount. The use amounts were (in ppm2.) : Sc, 0.12; Cr, 0.02; La.0.40;; Sm. 0.80; Eu, 0.036:TB, 1.20; Dy, 1.20; Tm. 0.08; Tb, 0.12; and Ba, 0.008. The use amount was one-fifth of the concentration required for activation analysis. Mortality and morbidity were negligible. No consistent growth rate changes were observed; however, different groups showed different growth rates during different generations. The number of mice born showed no significant differences amoung treatment groups. Survival, growth rate, hematology, morphological development, maturation, reproduction, and lactational performance were comparable in mice fed the different levels of 10 heavy metal oxides to those mice fed the basal diet.