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Upconverting stimulated emission depletion microscopy (U‐STED) is emerging as an effective approach for super‐resolution imaging due to its significantly low depletion power and its ability to surpass the limitations of the square‐root law and achieve higher resolution. Though the compelling performance, a trade‐off between the spatial resolution and imaging quality in U‐STED has been recognized in restricting the usability due to the low excitation power drove high depletion efficiency. Moreover, it is a burden to search for the right power relying on trial and error as the underpinning mechanism is unknown. Here, a method is proposed that can easily predict the ideal excitation power for high depletion efficiency with the assistance of the non‐saturate excitation based on the dynamic cross‐relaxation (CR) energy transfer of upconversion nanoparticles. This allows the authors to employ the rate equation model to simulate the populations of each relevant energy state of lanthanides and predict the ideal excitation power for high depletion efficiency. The authors demonstrate that the resolution of STED with the assistance of nonsaturated confocal super‐resolution results can easily achieve the highest resolution of sub‐40 nm, 1/24th of the excitation wavelengths. The finding on the CR effect provides opportunities for population control in realizing low‐power high‐resolution nanoscopy. [ABSTRACT FROM AUTHOR]

Preeclampsia is a heterogeneous and multiorgan cardiovascular disorder of pregnancy. Here, we report the development of a novel strip‐based lateral flow assay (LFA) using lanthanide‐doped upconversion nanoparticles conjugated to antibodies targeting two different biomarkers for detection of preeclampsia. We first measured circulating plasma FKBPL and CD44 protein concentrations from individuals with early‐onset preeclampsia (EOPE), using ELISA. We confirmed that the CD44/FKBPL ratio is reduced in EOPE with a good diagnostic potential. Using our rapid LFA prototypes, we achieved an improved lower limit of detection: 10 pg ml−1 for FKBPL and 15 pg ml−1 for CD44, which is more than one order lower than the standard ELISA method. Using clinical samples, a cut‐off value of 1.24 for CD44/FKBPL ratio provided positive predictive value of 100 % and the negative predictive value of 91 %. Our LFA shows promise as a rapid and highly sensitive point‐of‐care test for preeclampsia. [ABSTRACT FROM AUTHOR]

Sensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single‐molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo‐stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican‐1 (GPC‐1), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer. Under a wide‐field microscope, a single UCNP doped with thousands of lanthanide ions can emit sufficiently bright anti‐Stokes' luminescence to become quantitatively detectable. By counting every single streptavidin‐functionalized UCNP which specifically labeled on each sandwich immune complex across multiple fields of views, we achieved the Limit of Detection (LOD) of 0.0123 ng/ml, 0.2711 ng/ml, 0.1238 ng/ml, and 0.0158 ng/ml for GPC‐1, leptin, OPN and VEGF, respectively. The serum circulating level of GPC‐1, leptin, OPN, and VEGF in a mixture of 10 healthy normal human serum was 25.17 ng/ml, 18.04 ng/ml, 11.34 ng/ml, and 1.55 ng/ml, which was within the assay dynamic detection range for each analyte. Moreover, a 20% increase of GPC‐1 and OPN was observed by spiking the normal human serum with recombinant antigens to confirm the accuracy of the assay. We observed no cross‐reactivity among the four biomarker analytes, which eliminates the false positives and enhances the detection accuracy. The developed single upconversion nanoparticle‐assisted single‐molecule assay suggests its potential in clinical usage for prostate cancer detection by monitoring tiny concentration differences in a panel of serum biomarkers. [ABSTRACT FROM AUTHOR]

The facile hydrothermal synthesis of polyethyleneimine (PEI)-coated iron oxide (Fe3O4) nanoparticles (NPs) doped with Gd(OH)3 (Fe3O4-Gd(OH)3-PEI NPs) for dual mode T1- and T2-weighted magnetic resonance (MR) imaging applications is reported. In this approach, Fe3O4-Gd(OH)3-PEI NPs are synthesized via a hydrothermal method in the presence of branched PEI and Gd(III) ions. The PEI coating onto the particle surfaces enables further modification of poly(ethylene glycol) (PEG) in order to render the particles with good water dispersibility and improved biocompatibility. The formed Fe3O4-Gd(OH)3-PEI-PEG NPs have a Gd/Fe molar ratio of 0.25:1 and a mean particle size of 14.4 nm and display a relatively high r2 (151.37 × 10−3 m−1 s−1) and r1 (5.63 × 10−3 m−1 s−1) relaxivity, affording their uses as a unique contrast agent for T1- and T2-weighted MR imaging of rat livers after mesenteric vein injection of the particles and the mouse liver after intravenous injection of the particles, respectively. The developed Fe3O4-Gd(OH)3-PEI-PEG NPs may hold great promise to be used as a contrast agent for dual mode T1- and T2-weighted self-confirmation MR imaging of different biological systems. [ABSTRACT FROM AUTHOR]

This review reports the recent advances in dendrimer-entrapped metal colloids as contrast agents for biomedical imaging applications. The versatile dendrimer scaffolds with 3-dimensional spherical shape, highly branched internal cavity, tunable surface conjugation chemistry, and excellent biocompatibility and nonimmunogenicity afford their uses as templates to create multifunctional dendrimer-entrapped metal colloids for mono- or multi- mode molecular imaging applications. In particular, multifunctional dendrimer-entrapped gold nanoparticles with different surface modifications have been used for fluorescence imaging, targeted tumor computed tomography ( CT) imaging, enhanced blood pool CT imaging, dual mode CT/ MR imaging, and tumor theranostics (combined CT imaging and chemotherapy) will be introduced and discussed in detail. WIREs Nanomed Nanobiotechnol 2015, 7:678-690. doi: 10.1002/wnan.1331 For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

In this article, we report the surface modification of branched polyethyleneimine (PEI) for improved biocompatibility. PEIs with different surface functionalities were synthesized via covalent modification of the PEI amines, including neutralized PEI modified with acetic anhydride, negatively charged PEI modified with succinic anhydride, hydroxylated PEI modified with glycidol, and PEI-poly(ethylene glycol) (PEG) conjugates modified with both PEG and acetic anhydride. The modified PEI derivatives were characterized with 1H-NMR, Fourier transform infrared spectroscopy, and ζ-potential measurements. An in vitro cytotoxicity assay of mouse fibroblasts revealed that the biocompatibility of PEI was significantly improved after these modifications. The neutral and negatively charged PEIs were nontoxic at concentrations up to 200 μg/mL, whereas the pristine PEI was toxic to cells at concentrations as low as 10 μg/mL. The successfully modified PEIs with different surface charges and functionalities may provide a range of opportunities for various biomedical applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 [ABSTRACT FROM AUTHOR]

We report a facile approach to fabricating low-generation poly(amidoamine) (PAMAM) dendrimer-stabilized gold nanoparticles (Au DSNPs) functionalized with folic acid (FA) for in vitro and in vivo targeted computed tomography (CT) imaging of cancer cells. In this study, amine-terminated generation 2 PAMAM dendrimers were employed as stabilizers to form Au DSNPs without additional reducing agents. The formed Au DSNPs with an Au core size of 5.5 nm were covalently modified with the targeting ligand FA, followed by acetylation of the remaining dendrimer terminal amines to endow the particles with targeting specificity and improved biocompatibility. Our characterization data show that the formed FA-modified Au DSNPs are stable at different pH values (5-8) and temperatures (4-50 °C), as well as in different aqueous media. MTT assay data along with cell morphology observations reveal that the FA-modified Au DSNPs are noncytotoxic in the particle concentration range of 0-3000 n M. X-ray attenuation coefficient measurements show that the CT value of FA-modified Au DSNPs is much higher than that of Omnipaque (a clinically used CT contrast agent) at the same concentration of the radiodense elements (Au or iodine). Importantly, the FA-modified Au DSNPs are able to specifically target a model cancer cell line (KB cells, a human epithelial carcinoma cell line) over-expressing FA receptors and they enable targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo after intravenous administration of the particles. With the simple synthesis approach, easy modification, good cytocompatibility, and high X-ray attenuation coefficient, the FA-modified low-generation Au DSNPs could be used as promising contrast agents for targeted CT imaging of different tumors over-expressing FA receptors. [ABSTRACT FROM AUTHOR]