Jung Ho Yu

All Publications

• Highly Excretable Gold Supraclusters for Translatable In Vivo Raman Imaging of Tumors. ACS nano Yu, J. H., Jeong, M. S., Cruz, E. O., Alam, I. S., Tumbale, S. K., Zlitni, A., Lee, S. Y., Park, Y. I., Ferrara, K., Kwon, S., Gambhir, S. S., Rao, J. 2023

  Abstract

  Raman spectroscopy provides excellent specificity for in vivo preclinical imaging through a readout of fingerprint-like spectra. To achieve sufficient sensitivity for in vivo Raman imaging, metallic gold nanoparticles larger than 10 nm were employed to amplify Raman signals via surface-enhanced Raman scattering (SERS). However, the inability to excrete such large gold nanoparticles has restricted the translation of Raman imaging. Here we present Raman-active metallic gold supraclusters that are biodegradable and excretable as nanoclusters. Although the small size of the gold nanocluster building blocks compromises the electromagnetic field enhancement effect, the supraclusters exhibit bright and prominent Raman scattering comparable to that of large gold nanoparticle-based SERS nanotags due to high loading of NIR-resonant Raman dyes and much suppressed fluorescence background by metallic supraclusters. The bright Raman scattering of the supraclusters was pH-responsive, and we successfully performed in vivo Raman imaging of acidic tumors in mice. Furthermore, in contrast to large gold nanoparticles that remain in the liver and spleen over 4 months, the supraclusters dissociated into small nanoclusters, and 73% of the administered dose to mice was excreted during the same period. The highly excretable Raman supraclusters demonstrated here offer great potential for clinical applications of in vivo Raman imaging.

  View details for DOI 10.1021/acsnano.2c10378

  View details for PubMedID 36688431

• Vibrational Two-Photon Microscopy for Tissue Imaging: Short-Wave Infrared Surface-Enhanced Resonance Hyper-Raman Scattering. Journal of biophotonics Olson, J. E., Yu, J. H., Thimes, R. L., Camden, J. P. 2021: e202100158

  Abstract

  Multiphoton microscopies using short-wave infrared (SWIR) radiation offer nondestructive and high resolution imaging through tissue. Two-photon fluorescence, for example, is commonly employed to increase the penetration depth and spatial resolution of SWIR imaging, but the broad spectral peaks limits its multiplexing capabilities. Hyper-Raman scattering, the vibrational analog of two-photon fluorescence, yields spectral features on the order of 20 cm-1 and reporter-functionalized noble metal nanoparticles (NPs) provide a platform for both hyper-Raman signal enhancement and selective targeting in biological media. Herein we report the first tissue imaging study employing surface-enhanced resonance hyper-Raman scattering (SERHRS), the two-photon analog of surface-enhanced resonance Raman scattering. Specifically, we employ multicore gold-silica NPs (Au@SiO2 NPs) functionalized with a NIR-resonant cyanine dye, 3,3'-diethylthiatricarbocyanine iodide (DTTC) as a SERHRS reporter. SWIR SERHRS spectra are efficiently acquired from mouse spleen tissue. SWIR SERHRS combines two-photon imaging advantages with narrow vibrational peak widths, presenting future applications of multitargeted bioimaging. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbio.202100158

  View details for PubMedID 34609064

• Noninvasive and Highly Multiplexed Five-Color Tumor Imaging of Multicore Near-Infrared Resonant Surface-Enhanced Raman Nanoparticles In Vivo. ACS nano Yu, J. H., Steinberg, I., Davis, R. M., Malkovskiy, A. V., Zlitni, A., Radzyminski, R. K., Jung, K. O., Chung, D. T., Curet, L. D., D'Souza, A. L., Chang, E., Rosenberg, J., Campbell, J., Frostig, H., Park, S. M., Pratx, G., Levin, C., Gambhir, S. S. 2021

  Abstract

  In vivo multiplexed imaging aims for noninvasive monitoring of tumors with multiple channels without excision of the tissue. While most of the preclinical imaging has provided a number of multiplexing channels up to three, Raman imaging with surface-enhanced Raman scattering (SERS) nanoparticles was suggested to offer higher multiplexing capability originating from their narrow spectral width. However, in vivo multiplexed SERS imaging is still in its infancy for multichannel visualization of tumors, which require both sufficient multiplicity and high sensitivity concurrently. Here we create multispectral palettes of gold multicore-near-infrared (NIR) resonant Raman dyes-silica shell SERS (NIR-SERRS) nanoparticle oligomers and demonstrate noninvasive and five-plex SERS imaging of the nanoparticle accumulation in tumors of living mice. We perform the five-plex ratiometric imaging of tumors by varying the administered ratio of the nanoparticles, which simulates the detection of multiple biomarkers with different expression levels in the tumor environment. Furthermore, since this method does not require the excision of tumor tissues at the imaging condition, we perform noninvasive and longitudinal imaging of the five-color nanoparticles in the tumors, which is not feasible with current ex vivo multiplexed tissue analysis platforms. Our work surpasses the multiplicity limit of previous preclinical tumor imaging methods while keeping enough sensitivity for tumor-targeted in vivo imaging and could enable the noninvasive assessment of multiple biological targets within the tumor microenvironment in living subjects.

  View details for DOI 10.1021/acsnano.1c07470

  View details for PubMedID 34797988

• Vertical Heterostructure of Two-Dimensional MoS2 and WSe2 with Vertically Aligned Layers. Nano letters Yu, J. H., Lee, H. R., Hong, S. S., Kong, D., Lee, H., Wang, H., Xiong, F., Wang, S., Cui, Y. 2015; 15 (2): 1031-1035

  Abstract

  Two-dimensional (2D) layered materials consist of covalently bonded 2D atomic layers stacked by van der Waals interactions. Such anisotropic bonding nature gives rise to the orientation-dependent functionalities of the 2D layered materials. Different from most studies of 2D materials with their atomic layers parallel to substrate, we have recently developed layer vertically aligned 2D material nanofilms. Built on these developments, here, we demonstrate the synthesis of vertical heterostructure of n-type MoS2 and p-type WSe2 with vertically aligned atomic layers. Thin film of MoS2/WSe2 vertical structure was successfully synthesized without significant alloy formation. The heterostructure synthesis is scalable to a large area over 1 cm(2). We demonstrated the pn junction diode behavior of the heterostructure device. This novel device geometry opens up exciting opportunities for a variety of electronic and optoelectronic devices, complementary to the recent interesting vertical heterostructures with horizontal atomic layers.

  View details for DOI 10.1021/nl503897h

  View details for PubMedID 25590995

• High-resolution three-photon biomedical imaging using doped ZnS nanocrystals NATURE MATERIALS Yu, J. H., Kwon, S., Petrasek, Z., Park, O. K., Jun, S. W., Shin, K., Choi, M., Il Park, Y., Park, K., Na, H. B., Lee, N., Lee, D. W., Kim, J. H., Schwille, P., Hyeon, T. 2013; 12 (4): 359-366

  View details for DOI 10.1038/NMAT3565

  View details for Web of Science ID 000317164900026

• Giant Zeeman splitting in nucleation-controlled doped CdSe:Mn2+ quantum nanoribbons NATURE MATERIALS Yu, J. H., Liu, X., Kweon, K. E., Joo, J., Park, J., Ko, K., Lee, D., Shen, S., Tivakornsasithorn, K., Son, J. S., Park, J., Kim, Y., Hwang, G. S., Dobrowolska, M., Furdyna, J. K., Hyeon, T. 2010; 9 (1): 47-53

  Abstract

  Doping of semiconductor nanocrystals by transition-metal ions has attracted tremendous attention owing to their nanoscale spintronic applications. Such doping is, however, difficult to achieve in low-dimensional strongly quantum confined nanostructures by conventional growth procedures. Here we demonstrate that the incorporation of manganese ions up to 10% into CdSe quantum nanoribbons can be readily achieved by a nucleation-controlled doping process. The cation-exchange reaction of (CdSe)(13) clusters with Mn(2+) ions governs the Mn(2+) incorporation during the nucleation stage. This highly efficient Mn(2+) doping of the CdSe quantum nanoribbons results in giant exciton Zeeman splitting with an effective g-factor of approximately 600, the largest value seen so far in diluted magnetic semiconductor nanocrystals. Furthermore, the sign of the s-d exchange is inverted to negative owing to the exceptionally strong quantum confinement in our nanoribbons. The nucleation-controlled doping strategy demonstrated here thus opens the possibility of doping various strongly quantum confined nanocrystals for diverse applications.

  View details for DOI 10.1038/NMAT2572

  View details for Web of Science ID 000272854800018

  View details for PubMedID 19915554

• A mountable toilet system for personalized health monitoring via the analysis of excreta. Nature biomedical engineering Park, S. M., Won, D. D., Lee, B. J., Escobedo, D. n., Esteva, A. n., Aalipour, A. n., Ge, T. J., Kim, J. H., Suh, S. n., Choi, E. H., Lozano, A. X., Yao, C. n., Bodapati, S. n., Achterberg, F. B., Kim, J. n., Park, H. n., Choi, Y. n., Kim, W. J., Yu, J. H., Bhatt, A. M., Lee, J. K., Spitler, R. n., Wang, S. X., Gambhir, S. S. 2020

  Abstract

  Technologies for the longitudinal monitoring of a person's health are poorly integrated with clinical workflows, and have rarely produced actionable biometric data for healthcare providers. Here, we describe easily deployable hardware and software for the long-term analysis of a user's excreta through data collection and models of human health. The 'smart' toilet, which is self-contained and operates autonomously by leveraging pressure and motion sensors, analyses the user's urine using a standard-of-care colorimetric assay that traces red-green-blue values from images of urinalysis strips, calculates the flow rate and volume of urine using computer vision as a uroflowmeter, and classifies stool according to the Bristol stool form scale using deep learning, with performance that is comparable to the performance of trained medical personnel. Each user of the toilet is identified through their fingerprint and the distinctive features of their anoderm, and the data are securely stored and analysed in an encrypted cloud server. The toilet may find uses in the screening, diagnosis and longitudinal monitoring of specific patient populations.

  View details for DOI 10.1038/s41551-020-0534-9

  View details for PubMedID 32251391

• Whole-body tracking of single cells via positron emission tomography. Nature biomedical engineering Jung, K. O., Kim, T. J., Yu, J. H., Rhee, S. n., Zhao, W. n., Ha, B. n., Red-Horse, K. n., Gambhir, S. S., Pratx, G. n. 2020

  Abstract

  In vivo molecular imaging can measure the average kinetics and movement routes of injected cells through the body. However, owing to non-specific accumulation of the contrast agent and its efflux from the cells, most of these imaging methods inaccurately estimate the distribution of the cells. Here, we show that single human breast cancer cells loaded with mesoporous silica nanoparticles concentrating the 68Ga radioisotope and injected into immunodeficient mice can be tracked in real time from the pattern of annihilation photons detected using positron emission tomography, with respect to anatomical landmarks derived from X-ray computed tomography. The cells travelled at an average velocity of 50 mm s-1 and arrested in the lungs 2-3 s after tail-vein injection into the mice, which is consistent with the blood-flow rate. Single-cell tracking could be used to determine the kinetics of cell trafficking and arrest during the earliest phase of the metastatic cascade, the trafficking of immune cells during cancer immunotherapy and the distribution of cells after transplantation.

  View details for DOI 10.1038/s41551-020-0570-5

  View details for PubMedID 32541917

• Development and MPI tracking of novel hypoxia-targeted theranostic exosomes. Biomaterials Jung, K. O., Jo, H., Yu, J. H., Gambhir, S. S., Pratx, G. 2018; 177: 139–48

  Abstract

  Treating the hypoxic region of the tumor remains a significant challenge. The goals of this study are to develop an exosome platform that can target regions of tumor hypoxia and that can be monitored invivo using magnetic particle imaging (MPI). Four types of exosomes (generated under hypoxic or normoxic conditions, and with or without exposure to X-ray radiation) were isolated from MDA-MB-231 human breast cancer cells. Exosomes were labeled by DiO, a fluorescent lipophilic tracer, to quantify their uptake by hypoxic cancer cells. Subsequently, the exosomes were modified to carry SPIO (superparamagnetic iron oxide) nanoparticles and Olaparib (PARP inhibitor). FACS and fluorescence microscopy showed that hypoxic cells preferentially take up exosomes released by hypoxic cells, compared with other exosome formulations. In addition, the distribution of SPIO-labeled exosomes was successively imaged invivo using MPI. Finally, the therapeutic efficacy of Olaparib-loaded exosomes was demonstrated by increased apoptosis and slower tumor growth invivo. Our novel theranostic platform could be used as an effective strategy to monitor exosomes invivo and deliver therapeutics to hypoxic tumors.

  View details for PubMedID 29890363

• Towards clinically translatable in vivo nanodiagnostics Nature Reviews Materials Park, S., Aalipour, A., Vermesh, O., Yu, J., Gambhir, S. S. 2017; 2

  View details for DOI 10.1038/natrevmats.2017.14

• Two-dimensional limit of crystalline order in perovskite membrane films. Science advances Hong, S. S., Yu, J. H., Lu, D. n., Marshall, A. F., Hikita, Y. n., Cui, Y. n., Hwang, H. Y. 2017; 3 (11): eaao5173

  Abstract

  Long-range order and phase transitions in two-dimensional (2D) systems-such as magnetism, superconductivity, and crystallinity-have been important research topics for decades. The issue of 2D crystalline order has reemerged recently, with the development of exfoliated atomic crystals. Understanding the dimensional limit of crystalline phases, with different types of bonding and synthetic techniques, is at the foundation of low-dimensional materials design. We study ultrathin membranes of SrTiO3, an archetypal perovskite oxide with isotropic (3D) bonding. Atomically controlled membranes are released after synthesis by dissolving an underlying epitaxial layer. Although all unreleased films are initially single-crystalline, the SrTiO3 membrane lattice collapses below a critical thickness (5 unit cells). This crossover from algebraic to exponential decay of the crystalline coherence length is analogous to the 2D topological Berezinskii-Kosterlitz-Thouless (BKT) transition. The transition is likely driven by chemical bond breaking at the 2D layer-3D bulk interface, defining an effective dimensional phase boundary for coherent crystalline lattices.

  View details for PubMedID 29167822

  View details for PubMedCentralID PMC5696264

• In situ observation of divergent phase transformations in individual sulfide nanocrystals. Nano letters McDowell, M. T., Lu, Z., Koski, K. J., Yu, J. H., Zheng, G., Cui, Y. 2015; 15 (2): 1264-1271

  Abstract

  Inorganic nanocrystals have attracted widespread attention both for their size-dependent properties and for their potential use as building blocks in an array of applications. A complete understanding of chemical transformations in nanocrystals is important for controlling structure, composition, and electronic properties. Here, we utilize in situ high-resolution transmission electron microscopy to study structural and morphological transformations in individual sulfide nanocrystals (copper sulfide, iron sulfide, and cobalt sulfide) as they react with lithium. The experiments reveal the influence of structure and composition on the transformation pathway (conversion versus displacement reactions), and they provide a high-resolution view of the unique displacement reaction mechanism in copper sulfide in which copper metal is extruded from the crystal. The structural similarity between the initial and final phases, as well as the mobility of ions within the crystal, are seen to exert a controlling influence on the reaction pathway.

  View details for DOI 10.1021/nl504436m

  View details for PubMedID 25602713

• Two-dimensional layered transition metal disulphides for effective encapsulation of high-capacity lithium sulphide cathodes NATURE COMMUNICATIONS Seh, Z. W., Yu, J. H., Li, W., Hsu, P., Wang, H., Sun, Y., Yao, H., Zhang, Q., Cui, Y. 2014; 5

  Abstract

  Fully lithiated lithium sulphide (Li2S) is currently being explored as a promising cathode material for emerging energy storage applications. Like their sulphur counterparts, Li2S cathodes require effective encapsulation to reduce the dissolution of intermediate lithium polysulphide (Li2Sn, n=4-8) species into the electrolyte. Here we report, the encapsulation of Li2S cathodes using two-dimensional layered transition metal disulphides that possess a combination of high conductivity and strong binding with Li2S/Li2Sn species. In particular, using titanium disulphide as an encapsulation material, we demonstrate a high specific capacity of 503 mAh g(-1)(Li2S) under high C-rate conditions (4C) as well as high areal capacity of 3.0 mAh cm(-2) under high mass-loading conditions (5.3 mg(Li2S) cm(-2)). This work opens up the new prospect of using transition metal disulphides instead of conventional carbon-based materials for effective encapsulation of high-capacity electrode materials.

  View details for DOI 10.1038/ncomms6017

  View details for Web of Science ID 000342985900004

• Magnetic fluorescent delivery vehicle using uniform mesoporous silica spheres embedded with monodisperse magnetic and semiconductor nanocrystals JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Kim, J., Lee, J. E., Lee, J., Yu, J. H., Kim, B. C., An, K., Hwang, Y., Shin, C. H., Park, J. G., Kim, J., Hyeon, T. 2006; 128 (3): 688-689

  Abstract

  We synthesized uniform pore-sized mesoporous silica spheres embedded with magnetite nanocrystal and quantum dots. The magnetic separation, luminescent detection, and controlled release of drugs were demonstrated using the uniform mesoporous silica spheres embedded with monodisperse nanocrystals.

  View details for Web of Science ID 000234815000010

  View details for PubMedID 16417336