Sheng Yao Dai

All Publications

• Mycobacteriophage Functionalized Magnetic Nanocrystal Clusters for Highly Sensitive and Rapid Detection of Mycobacterium tuberculosis. JACS Au Xiao, Z., Yen, C., Wang, T., Ibrahim, J., Fu, Q., Dai, S. Y., Hajfathalian, M., Murugesan, K., Banaei, N., Bogyo, M., Rao, J. 2025; 5 (12): 6100-6111

  Abstract

  Tuberculosis caused by Mycobacterium tuberculosis (Mtb) is one of the most dangerous diseases globally. Mtb poses a heavy death toll, especially in low-resource settings, where inadequate diagnostic capabilities greatly hinder treatment and prevention. Here, we present a rapid and cost-effective bacilli-capturing method that uses magnetic nanoclusters conjugated with mycobacteriophages. The mycobacteriophages provide Mtb recognition functionality, and the binding of the nanoparticles with attenuated Mtb H37Rv and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) was visualized by electron microscopy. The magnetic nanocrystal clusters have an excellent separation efficiency. A nearly 100% capturing efficiency and high specificity toward mycobacteria species were obtained. Magnetically separated mycobacteria were disrupted by ultrasound to facilitate the rapid release of cellular adenosine triphosphate (ATP) for bioluminescent detection. Using portable and inexpensive devices, we achieved rapid detection of Mtb at as low as 1000 bacilli per sample in artificial sputum, urine, and whole porcine blood within 35 min. This method demonstrates excellent potential for point-of-care tuberculosis diagnosis in resource-limited settings.

  View details for DOI 10.1021/jacsau.5c01050

  View details for PubMedID 41450655

  View details for PubMedCentralID PMC12728615

• Mycobacteriophage Functionalized Magnetic Nanocrystal Clusters for Highly Sensitive and Rapid Detection of Mycobacterium tuberculosis JACS AU Xiao, Z., Yen, C., Wang, T., Ibrahim, J., Fu, Q., Dai, S., Hajfathalian, M., Murugesan, K., Banaei, N., Bogyo, M., Rao, J. 2025

  View details for DOI 10.1021/jacsau.5c01050

  View details for Web of Science ID 001628381200001

• B7-H4 ImmunoPET Imaging Tracks Tumor-Associated Macrophage Changes in Prostate Cancer. Molecular pharmaceutics Kumar, M., Singh, S. B., Vasyliv, I., Habte, F., Kalita, M., Alam, I. S., Koladiya, A., Dai, S. Y., James, M., Rao, J., Beziere, N., Daldrup-Link, H. E. 2025

  Abstract

  B7-H4 is an inhibitory immune checkpoint molecule that is upregulated in various cancers and correlates with advanced tumor stages and poor clinical outcomes. This study aimed to develop an immunoPET radiotracer for noninvasive assessment of B7-H4 expression in tumors and tumor-associated macrophages (TAM) and to evaluate the radiotracer potential to monitor therapeutic responses. We generated a B7-H4-targeted immunoPET imaging tracer by radiolabeling the anti-B7-H4 monoclonal antibody (2H9) with [89Zr], yielding [89Zr]Zr-DFO-2H9, and assessed its biodistribution in prostate cancer xenografts to quantitatively measure B7-H4 expression in vivo. In vitro binding studies confirmed the retained immunoreactivity and specificity for B7-H4. Radiochemical purity was verified using size exclusion chromatography. In vivo evaluation of [89Zr]Zr-DFO-2H9 was first performed in immunodeficient nude mice bearing subcutaneous DU145 human prostate tumors, with longitudinal PET imaging conducted over 7 days postinjection, followed by terminal biodistribution analysis. [89Zr]Zr-DFO-2H9 demonstrated a good tumor-binding profile and specificity in DU145 tumor xenografts. To distinguish PET signals from tumor cells versus macrophages, immunocompetent C57BL/6 mice bearing syngeneic TRAMP-C2 prostate tumors were divided into three cohorts and treated with PBS (control), cold anti-B7-H4 mAb (for B7-H4 blockade), or clodronate liposome (for macrophage depletion). In TRAMP-C2 tumors, the PET signal was significantly reduced in both the B7-H4 blocked and macrophage-depleted group compared to controls. Immunohistochemistry revealed that B7-H4 expression differences among TRAMP-C2 treatment groups were not as clearly distinguishable as those observed in vivo via PET imaging. Multiplexed immunofluorescence staining of macrophage markers indicated that infiltrating TAMs were the major contributors to B7-H4-specific PET signals within the tumor stroma. Collectively, these results show that [89Zr]Zr-DFO-2H9 binds B7-H4 with high affinity and specificity and reflects changes in TAM levels in vivo. The new radiotracer shows promise for detecting B7-H4 positive tumors and TAM levels, profiling the immune microenvironment, and monitoring macrophage-targeted immunotherapies.

  View details for DOI 10.1021/acs.molpharmaceut.5c00637

  View details for PubMedID 41122911

• Light-Controlled Intracellular Synthesis of Poly(luciferin) Polymers Induces Cell Paraptosis. Journal of the American Chemical Society Dai, S., Xiao, Z., Shen, F., Lim, I., Rao, J. 2025

  Abstract

  Accumulation of misfolded proteins challenges cellular proteostasis and is implicated in aging and chronic disorders. Cancer cells, moreover, face an elevated level of basal proteotoxic stress; hence, exacerbating endoplasmic reticulum (ER) stress has been shown to induce programmed cell death while enhancing anticancer immunogenicity. We hypothesize that hydrophobic abiotic macromolecules can trigger a similar stress response. Most polymers and nanoparticles, however, are sequestered in endo/lysosomes after endocytosis, which prevents their interaction with the proteostasis machinery. We adopted an in situ polymerization approach to synthesize polymers in cells with cell-permeable monomers. Specifically, we developed a biocompatible polycondensation between l-cysteine and 2-cyanobenzothiazole (CBT) with photochemical control to form insoluble poly(luciferin) aggregates. We identified that in situ polymerization activates the BiP-PERK-CHOP pathway of the unfolded protein response and that the unresolved ER stress initiates a form of regulated cell death consistent with paraptosis. In addition, the dying cells emit damage-associated molecular patterns (DAMPs), indicating an immunogenic cell death that could potentiate antitumor immunity. Our results show that in situ polymerization mimics misfolded protein aggregates to induce proteotoxic stress and cancer cell death, offering a novel therapeutic strategy to exploit cancer vulnerability.

  View details for DOI 10.1021/jacs.4c15644

  View details for PubMedID 39757486

• Invivo bioluminescence imaging of granzyme B activity in tumor response to cancer immunotherapy. Cell chemical biology Chen, M., Zhou, K., Dai, S., Tadepalli, S., Balakrishnan, P. B., Xie, J., Rami, F. E., Dai, T., Cui, L., Idoyaga, J., Rao, J. 2022

  Abstract

  Cancer immunotherapy has revolutionized the treatment of cancer, but only a small subset of patients benefits from this new treatment regime. Imaging tools are useful for early detection of tumor response to immunotherapy and probing the dynamic and complex immune system. Here, we report a bioluminescence probe (GBLI-2) for non-invasive, real-time, longitudinal imaging of granzyme B activity in tumors receiving immune checkpoint inhibitors. GBLI-2 is made of the mouse granzyme B tetrapeptide IEFD substrate conjugated to D-luciferin through a self-immolative group. GBLI-2 was evaluated for imaging the dynamics of the granzyme B activity and predicting therapeutic efficacy in a syngeneic mouse model of CT26 murine colorectal carcinoma. The GBLI-2 signal correlated with the change in the population of PD-1- and granzyme B-expressing CD8+ Tcells in tumors.

  View details for DOI 10.1016/j.chembiol.2022.08.006

  View details for PubMedID 36103874

• Multiparameter Longitudinal Imaging of Immune Cell Activity in Chimeric Antigen Receptor T Cell and Checkpoint Blockade Therapies. ACS central science Xie, J., El Rami, F., Zhou, K., Simonetta, F., Chen, Z., Zheng, X., Chen, M., Balakrishnan, P. B., Dai, S., Murty, S., Alam, I. S., Baker, J., Negrin, R. S., Gambhir, S. S., Rao, J. 2022; 8 (5): 590-602

  Abstract

  Longitudinal multimodal imaging presents unique opportunities for noninvasive surveillance and prediction of treatment response to cancer immunotherapy. In this work we first designed a novel granzyme B activated self-assembly small molecule, G-SNAT, for the assessment of cytotoxic T lymphocyte mediated cancer cell killing. G-SNAT was found to specifically detect the activity of granzyme B within the cytotoxic granules of activated T cells and engaged cancer cells in vitro. In lymphoma tumor-bearing mice, the retention of cyanine 5 labeled G-SNAT-Cy5 correlated to CAR T cell mediated granzyme B exocytosis and tumor eradication. In colorectal tumor-bearing transgenic mice with hematopoietic cells expressing firefly luciferase, longitudinal bioluminescence and fluorescence imaging revealed that after combination treatment of anti-PD-1 and anti-CTLA-4, the dynamics of immune cell trafficking, tumor infiltration, and cytotoxic activity predicted the therapeutic outcome before tumor shrinkage was evident. These results support further development of G-SNAT for imaging early immune response to checkpoint blockade and CAR T-cell therapy in patients and highlight the utility of multimodality imaging for improved mechanistic insights into cancer immunotherapy.

  View details for DOI 10.1021/acscentsci.2c00142

  View details for PubMedID 35647285

• A Sm(II)-Mediated Cascade Approach to Dibenzoindolo[3,2-<i>b</i>]carbazoles: Synthesis and Evaluation ORGANIC LETTERS Levick, M. T., Grace, I., Dai, S., Kasch, N., Muryn, C., Lambert, C., Turner, M. L., Procter, D. J. 2014; 16 (8): 2292-2295

  Abstract

  Previously unstudied dibenzoindolo[3,2-b]carbazoles have been prepared by two-directional, phase tag-assisted synthesis utilizing a connective-Pummerer cyclization and a SmI2-mediated tag cleavage-cyclization cascade. The use of a phase tag allows us to exploit unstable intermediates that would otherwise need to be avoided. The novel materials were characterized by X-ray, cyclic voltammetry, UV-vis spectroscopy, TGA, and DSC. Preliminary studies on the performance of OFET devices are also described.

  View details for DOI 10.1021/ol500841b

  View details for Web of Science ID 000334823600056

  View details for PubMedID 24712719