Junhan (Selene) Zhou

All Publications

• Magnetic resonance imaging of tumor-associated-macrophages (TAMs) with a nanoparticle contrast agent RSC ADVANCES Zhou, J., Meli, V. S., Yu-Tin Chen, E., Kapre, R., Nagalla, R., Xiao, W., Borowsky, A. D., Lam, K. S., Liu, W. F., Louie, A. Y. 2022; 12 (13): 7742-7756

  Abstract

  In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment. Imaging has the potential for three-dimensional mapping; however, there is a paucity of macrophage-targeted contrast agents to specifically detect TAM subtypes. We have previously found that sulfated-dextran coated iron oxide nanoparticles (SDIO) can target macrophage scavenger receptor A (SR-A, also known as CD204). Since CD204 (SR-A) is considered a biomarker for the M2 macrophage polarization, these SDIO might provide M2-specific imaging probes for MRI. In this work, we investigate whether SDIO can label M2-polarized cells in vitro. We evaluate the effect of degree of sulfation on uptake by primary cultured bone marrow derived macrophages (BMDM) and found that a higher degree of sulfation led to higher uptake, but there were no differences across the subtypes. Further analysis of the BMDM showed similar SR-A expression across stimulation conditions, suggesting that this classic model for macrophage subtypes may not be ideal for definitive M2 subtype marker expression, especially SR-A. We further examine the localization of SDIO in TAMs in vivo, in the mammary fat pad mouse model of breast cancer. We demonstrate that uptake by TAMs expressing SR-A scales with degree of sulfation, consistent with the in vitro studies. The TAMs demonstrate M2-like function and secrete Arg-1 but not iNOS. Uptake by these M2-like TAMs is validated by immunohistochemistry. SDIO show promise as a valuable addition to the toolkit of imaging probes targeted to different biomarkers for TAMs.

  View details for DOI 10.1039/d1ra08061j

  View details for Web of Science ID 000765903700001

  View details for PubMedID 35424752

  View details for PubMedCentralID PMC8982161

• Click-Ready Perfluorocarbon Nanoemulsion for <SUP>19</SUP>F MRI and Multimodal Cellular Detection ACS NANOSCIENCE AU Perez, A. S., Zhou, J., Leach, B., Xu, H., Lister, D., Adams, S. R., Ahrens, E. T., Louie, A. Y. 2021; 2 (2): 102-110

  Abstract

  We describe an in vivo imaging probe platform that is readily modifiable to accommodate binding of different molecular targeting moieties and payloads for multimodal image generation. In this work, we demonstrate the utility of perfluorocarbon (PFC) nanoemulsions incorporating dibenzocyclooctyne (DBCO) by enabling postemulsification functionalization via a click reaction with azide-containing ligands. The addition of DBCO-lipid to the surfactant in PFC nanoemulsions did not affect nanoemulsion size or nanoemulsion stability. As proof-of-concept, fluorescent dye-azides were conjugated to PFC nanoemulsions, demonstrating the feasibility of functionalization the by click reaction. Uptake of the fluorescent PFC by macrophages was demonstrated both in vitro in cultured macrophages and in situ in an acute inflammation mouse model, where fluorescence imaging and 1H/19F magnetic resonance imaging (MRI) were used for in vivo detection. Overall, these data demonstrate the potential of PFC nanoemulsions incorporating DBCO as a versatile platform for generating functionalized probes.

  View details for DOI 10.1021/acsnanoscienceau.1c00016

  View details for Web of Science ID 001027126300001

  View details for PubMedID 35481225

  View details for PubMedCentralID PMC9026270

• Synthesis and Comparative Evaluation of Photoswitchable Magnetic Resonance Imaging Contrast Agents ACS OMEGA Gao, M., Shen, B., Zhou, J., Kapre, R., Louie, A. Y., Shaw, J. T. 2020; 5 (24): 14759-14766

  Abstract

  A series of spiropyran (SP)-based magnetic resonance imaging (MRI) contrast agents have been synthesized and evaluated for changes in relaxivity resulting from irradiation with visible light. Both electron-donating and electron-withdrawing substituents were appended to the SP ring in order to study the electronic effects on the photochromic and relaxivity properties of these photoswitchable MRI contrast agents. Photoswitches lacking an electron-withdrawing substituent isomerize readily between the merocyanine and SP forms, while the addition of a nitro group prevents this process. Complexes capable of isomerizing were demonstrated to effect a change in the relaxivity of the appended gadolinium complex.

  View details for DOI 10.1021/acsomega.0c01534

  View details for Web of Science ID 000543740600058

  View details for PubMedID 32596613

  View details for PubMedCentralID PMC7315594

• Effect of Structure and Intramolecular Distances on Photoswitchable Magnetic Resonance Imaging Contrast Agents JOURNAL OF ORGANIC CHEMISTRY Shen, B., Gao, M., Franco, F., Kapre, R., Zhou, J., Li, X., Garcia, J., Shaw, J. T., Louie, A. Y. 2020; 85 (11): 7333-7341

  Abstract

  Light-activated sensors are of great interest for biological applications but are limited by the depth of penetration of light. We have been interested in transducing light activation to a magnetic signal that can be detected through noninvasive imaging by magnetic resonance imaging (MRI). We have previously developed agents incorporating spiropyran derivatives as the sensing moiety and characterized features that influence photoswitching; however, we found the MRI response to be unpredictable. In this work, we delve deeper into the potential mechanisms for the observed MRI responses in an effort to better understand the structural effects on controlling magnetic properties. A series of light-activatable MRI contrast agents were synthesized and characterized to assess the effect of spiropyran positioning on contrast agent functions and properties. These compounds are based on the same spiropyran skeleton, also named 1',3',3'-trimethyl-6-nitrospiro[chromene-2,2-indoline], which is linked with an MRI contrast agent, gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (DO3A). We investigated the photo-to-magnetic conversion properties of these novel compounds by adjusting linker lengths over a range from three to seven methylene groups. The primary results indicated that the contrast agent with a five-carbon linker (25) showed the highest light-sensing ability after irradiation with visible light. The results will aid in the design of future spiropyran-based MRI sensors.

  View details for DOI 10.1021/acs.joc.0c00706

  View details for Web of Science ID 000538764000046

  View details for PubMedID 32397710

• A novel gamma GLM approach to MRI relaxometry comparisons MAGNETIC RESONANCE IN MEDICINE Kapre, R., Zhou, J., Li, X., Beckett, L., Louie, A. Y. 2020; 84 (3): 1592-1604

  Abstract

  To demonstrate that constant coefficient of variation (CV), but nonconstant absolute variance in MRI relaxometry (T1 , T2 , R1 , R2 ) data leads to erroneous conclusions based on standard linear models such as ordinary least squares (OLS). We propose a gamma generalized linear model identity link (GGLM-ID) framework that factors the inherent CV into parameter estimates. We first examined the effects on calculations of contrast agent relaxivity before broadening to other applications such as analysis of variance (ANOVA) and liver iron content (LIC).Eight models including OLS and GGLM-ID were initially fit to data obtained on sulfated dextran iron oxide (SDIO) nanoparticles. Both a resampling simulation on the data as well as two separate Monte Carlo simulations (with and without concentration error) were performed to determine mean square error (MSE) and type I error rate. We then evaluated the performance of OLS/GGLM-ID on R1 repeatability and LIC data sets.OLS had an MSE of 4-5× that of GGLM-ID as well as a type I error rate of 20-30%, whereas GGLM-ID was near the nominal 5% level in the relaxivity study. Only OLS found statistically significant effects of MRI facility on relaxivity in an R1 repeatability study, but no significant differences were found in a resampling, whereas GGLM was more consistent. GGLM-ID was also superior to OLS for modeling LIC.OLS leads to erroneous conclusions when analyzing MRI relaxometry data. GGLM-ID factors in the inherent CV of an MRI experiment, leading to more reproducible conclusions.

  View details for DOI 10.1002/mrm.28192

  View details for Web of Science ID 000512821800001

  View details for PubMedID 32048764

  View details for PubMedCentralID PMC7317199

• Metallosurfactant Ionogels in Imidazolium and Protic Ionic Liquids as Precursors To Synthesize Nanoceria as Catalase Mimetics for the Catalytic Decomposition of H₂O₂ CHEMISTRY-A EUROPEAN JOURNAL Wang, X., Yang, Q., Cao, Y., Hao, H., Zhou, J., Hao, J. 2016; 22 (49): 17857-17865

  Abstract

  The gelation behavior of cationic surfactants with different counterions, Br- , [FeCl3 Br]- , and [CeCl3 Br]- , in imidazolium ionic liquids (ILs) and protic ethylammonium nitrate was investigated. Small-angle X-ray scattering measurements and freeze-fracture transmission electron microscopy observations revealed the lamellar phases of metallosurfactant ionogels. The characteristics of imidazolium ILs, including the size and type, have effects on metallosurfactant ionogel properties, such as transformation temperatures, interlayer spacing, and mechanical strength. Cubic fluorite structured cerium oxide nanoparticles (CeO2 NPs) were produced by using metallosurfactant ionogels as precursors. Cubic fluorite CeO2 exhibited good catalase mimetic activity toward H2 O2 to generate O2 , providing more multiple mimetic enzyme activities of CeO2 NPs for H2 O2 .

  View details for DOI 10.1002/chem.201603743

  View details for Web of Science ID 000388471700044

  View details for PubMedID 27783445

• Ionogels of a Sugar Surfactant in Ionic Liquids CHEMISTRY-AN ASIAN JOURNAL Wang, X., Yang, Q., Cao, Y., Zhou, J., Hao, H., Liang, Y., Hao, J. 2016; 11 (5): 722-729

  Abstract

  Green and environmentally friendly ionogels formed by a sugar surfactant were prepared in two kinds of imidazolium-based ionic liquids. The phase transition from ribbon structures to lamellar structures induced by temperature and the transition mechanism were investigated in detail by means of freeze-fracture TEM and field-emission SEM observations, as well as small-angle X-ray scattering measurements. The rheological properties and tribological properties of two kinds of ionogels were systematically investigated. The difference in the lubricating properties and antiwear capability can be explained well by the mechanical and viscoelastic properties, as well as the different microstructures of samples destroyed by shear forces. This work provides a better understanding of the relationship between the structures, rheological properties, and tribological properties of ionogels.

  View details for DOI 10.1002/asia.201501198

  View details for Web of Science ID 000372184600014

  View details for PubMedID 26647361