624 results on '"Weibo Cai"'
Search Results
52. PET imaging of hepatocellular carcinoma by targeting tumor-associated endothelium using [68Ga]Ga-PSMA-617
- Author
-
Qiaomiao Lu, Yu Long, Kevin Fan, Zhiwen Shen, Yongkang Gai, Qingyao Liu, Dawei Jiang, Weibo Cai, Chidan Wan, and Xiaoli Lan
- Subjects
Glutamate Carboxypeptidase II ,Male ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Endothelial Cells ,Prostatic Neoplasms ,Gallium Radioisotopes ,Dipeptides ,General Medicine ,Prostate-Specific Antigen ,Heterocyclic Compounds, 1-Ring ,Cell Line, Tumor ,Positron-Emission Tomography ,Animals ,Humans ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,Endothelium - Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor associated with high morbidity and mortality rates. In many non-prostate solid tumors such as HCC, prostate-specific membrane antigens (PSMA) are overexpressed in tumor-associated endothelial cells. Therefore, the aim of this study was to evaluate the performance of [sup68/supGa]Ga-PSMA-617 PET imaging on HCC with different animal models, including cell line-derived xenografts (CDX) and patient-derived xenografts (PDX), and to explore its mechanisms of function.[sup68/supGa]Ga-PSMA-617 was prepared. The expression level of PSMA in two human hepatocellular cancer cells (HepG2 and HuH-7) was evaluated, and the cellular uptakes of [sup68/supGa]Ga-PSMA-617 were assayed. HepG2 and HuH-7 subcutaneous xenograft models, HepG2 orthotopic xenograft models, and four different groups of PDX models were prepared. Preclinical pharmacokinetics and performance of [sup68/supGa]Ga-PSMA-617 were evaluated in different types of HCC xenografts models using small animal PET and biodistribution studies.Low PSMA expression level of HepG2 and HuH-7 cells was observed, and the cellular uptake and blocking study confirmed the non-specificity of the PSMA-targeted probe binding to HepG2 and HuH-7 cells. In the subcutaneous xenograft models, the tumor uptakes at 0.5 h were 0.76 ± 0.12%ID/g (HepG2 tumors) and 0.78 ± 0.08%ID/g (HuH-7 tumors), respectively, which were significantly higher than those of the blocking groups (0.23 ± 0.04%ID/g and 0.20 ± 0.04%ID/g, respectively). In the orthotopic xenograft models, PET images clearly displayed the tumor locations based on the preferential accumulation of [sup68/supGa]Ga-PSMA-617 in tumor tissue versus normal liver tissue, suggesting the possibility of using [sup68/supGa]Ga-PSMA-617 PET imaging to detect primary HCC lesions in deep tissue. In the four different groups of HCC PDX models, PET imaging with [sup68/supGa]Ga-PSMA-617 provided clear tumor uptakes with prominent tumor-to-background contrast, further demonstrating its potential for the clinical imaging of PSMA-positive HCC lesions. The staining of tumor tissue sections with CD31- and PSMA-specific antibodies visualized the tumor-associated blood vessels and PSMA expression on endothelial cells in subcutaneous, orthotopic tissues, and PDX tissues, confirming the imaging with [sup68/supGa]Ga-PSMA-617 might be mediated by targeting tumor associated endothelium.In this study, in vivo PET on different types of HCC xenograft models illustrated high uptake within tumors, which confirmed that [sup68/supGa]Ga-PSMA-617 PET may be a promising imaging modality for HCC by targeting tumor associated endothelium.
- Published
- 2022
53. Figure S1 from Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer
- Author
-
Joshua M. Lang, Scott M. Dehm, Weibo Cai, Scott T. Tagawa, Manish Kohli, Shuang G. Zhao, Howard R. Soule, Susan F. Slovin, Christos E. Kyriakopoulos, Peng Huang, Jonathan W. Engle, Yanan Ren, Rendong Yang, Liewei Wang, Liguo Wang, Nicholas R. Rydzewski, Erika Heninger, David J. Niles, Katherine R. Kaufmann, Anupama Singh, Dawei Jiang, Charlotte N. Stahlfeld, Kyle T. Helzer, and Jamie M. Sperger
- Abstract
Figure S1. Correlation of TACSTD2 with Prostate Cancer Cell Surface Markers.
- Published
- 2023
54. Data from Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer
- Author
-
Joshua M. Lang, Scott M. Dehm, Weibo Cai, Scott T. Tagawa, Manish Kohli, Shuang G. Zhao, Howard R. Soule, Susan F. Slovin, Christos E. Kyriakopoulos, Peng Huang, Jonathan W. Engle, Yanan Ren, Rendong Yang, Liewei Wang, Liguo Wang, Nicholas R. Rydzewski, Erika Heninger, David J. Niles, Katherine R. Kaufmann, Anupama Singh, Dawei Jiang, Charlotte N. Stahlfeld, Kyle T. Helzer, and Jamie M. Sperger
- Abstract
Purpose:Men with metastatic castration-resistant prostate cancer (mCRPC) frequently develop resistance to androgen receptor signaling inhibitor (ARSI) treatment; therefore, new therapies are needed. Trophoblastic cell-surface antigen (TROP-2) is a transmembrane protein identified in prostate cancer and overexpressed in multiple malignancies. TROP-2 is a therapeutic target for antibody–drug conjugates (ADC).Experimental Design:TROP-2 gene (TACSTD2) expression and markers of treatment resistance from prostate biopsies were analyzed using data from four previously curated cohorts of mCRPC (n = 634) and the PROMOTE study (dbGaP accession phs001141.v1.p1, n = 88). EPCAM or TROP-2–positive circulating tumor cells (CTC) were captured from peripheral blood for comparison of protein (n = 15) and gene expression signatures of treatment resistance (n = 40). We assessed the efficacy of TROP-2–targeting agents in a mouse xenograft model generated from prostate cancer cell lines.Results:We demonstrated that TACSTD2 is expressed in mCRPC from luminal and basal tumors but at lower levels in patients with neuroendocrine prostate cancer. Patients previously treated with ARSI showed no significant difference in TACSTD2 expression, whereas patients with detectable AR-V7 expression showed increased expression. We observed that TROP-2 can serve as a cell surface target for isolating CTCs, which may serve as a predictive biomarker for ADCs. We also demonstrated that prostate cancer cell line xenografts can be targeted specifically by labeled anti–TROP-2 agents in vivo.Conclusions:These results support further studies on TROP-2 as a therapeutic and diagnostic target for mCRPC.
- Published
- 2023
55. Nanomaterial-based contrast agents
- Author
-
Jessica C. Hsu, Zhongmin Tang, Olga E. Eremina, Alexandros Marios Sofias, Twan Lammers, Jonathan F. Lovell, Cristina Zavaleta, Weibo Cai, and David P. Cormode
- Subjects
General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
56. Supplementary methods, Supplementary tables 1 through 4, and Supplementary figure 1 from Comparison of the Superagonist Complex, ALT-803, to IL15 as Cancer Immunotherapeutics in Animal Models
- Author
-
Hing C. Wong, Weibo Cai, Emily K. Jeng, Jonah B. Sacha, Sarah Alter, Sixiang Shi, Kaiping Han, Ana C. Edwards, Lin Kong, Lijing You, Jinghai Wen, Xiaoyun Zhu, Bai Liu, Xiaoyue Chen, Gabriela M. Webb, Hao Hong, Wenxin Xu, Jack O. Egan, and Peter R. Rhode
- Abstract
Supplementary methods. Supplementary Table S1. Antibodies used in immune cell characterization by flow cytometry. Supplementary Table S2. PK parameters of ALT-803 administered to cynomolgus monkeys. Supplementary Table S3. Representative clinical characteristics of cynomolgus monkeys following 4 weekly doses of ALT-803 administration (study day 26). Supplementary Table S4. Incidence of major histopathologic findings in cynomolgus monkeys following 4 weekly doses of ALT-803 administration (study day 26). Supplementary Figure 1. Comparative binding of ALT-803 to IL-15 receptors on mouse, cynomolgus monkey, and human immune cells.
- Published
- 2023
57. Movie S3 from Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of Pancreatic Cancer
- Author
-
Weibo Cai, Robert J. Nickles, Hing C. Wong, Charles P. Theuer, Bai Liu, Reinier Hernandez, Stephen A. Graves, Sixiang Shi, Christopher G. England, and Haiming Luo
- Abstract
Movie S3 from Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of Pancreatic Cancer
- Published
- 2023
58. Supplementary Methods from Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of Pancreatic Cancer
- Author
-
Weibo Cai, Robert J. Nickles, Hing C. Wong, Charles P. Theuer, Bai Liu, Reinier Hernandez, Stephen A. Graves, Sixiang Shi, Christopher G. England, and Haiming Luo
- Abstract
Determination of NOTA to Fab Fragment Ratio
- Published
- 2023
59. Data from Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein
- Author
-
Xiaoyuan Chen, Amir Kashefi, Lina He, Zibo Li, Weibo Cai, Kai Chen, and Hui Wang
- Abstract
This study used integrin αvβ3 as a target for tumor-specific delivery of tumor necrosis factor-α (TNF). The fusion protein RGD4C-TNF bound specifically to αvβ3 as evidenced by cell receptor binding assay and noninvasive micro-positron emission tomography imaging. 64Cu-DOTA-RGD4C-TNF had significantly higher activity accumulation in integrin-positive tumors (U87MG and MDA-MB-435) but not in integrin-negative tumors (C6) compared with 64Cu-DOTA-TNF. The magnitude of tumor uptake of 64Cu-DOTA-RGD4C-TNF correlated well with the αvβ3 level (U87MG > MDA-MB-435 > C6). Tumor accumulation of 64Cu-DOTA-RGD4C-TNF could be effectively blocked by c(RGDyK) peptide in αvβ3-positive tumor models, suggesting αvβ3 specificity of RGD4C-TNF fusion protein in vivo. Furthermore, although the fusion of RGD4C moiety to TNF had little effect on the bioactivity and cytotoxicity of RGD4C-TNF compared with TNF in cell culture, RGD4C-TNF was significantly more potent than TNF in inhibiting orthotopic MDA-MB-435 tumor growth. Ex vivo tissue staining confirmed specific cytotoxicity of RGD4C-TNF against integrin-positive tumor cells and tumor vasculature. [Mol Cancer Ther 2008;7(5):1044–53]
- Published
- 2023
60. Supplementary Figures from Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of Pancreatic Cancer
- Author
-
Weibo Cai, Robert J. Nickles, Hing C. Wong, Charles P. Theuer, Bai Liu, Reinier Hernandez, Stephen A. Graves, Sixiang Shi, Christopher G. England, and Haiming Luo
- Abstract
Supplementary Figure 1. Purification of heterodimer after click chemistry conjugation of ALT-836-Fab and TRC105-Fab Supplementary Figure 2. MALDI-TOF mass spectra of ALT-836-Fab: [M+H]+ = 47266.0, TRC105-Fab: [M+H]+ = 47454.7, and heterodimer: exact [M+H]+ = 103504.0. Supplementary Figure 3. Flow cytometry analysis in BXPC-3 after 1 h incubation of FITC-Fab conjugates for the comparison of their in vitro targeting Supplementary Figure 4. Radiolabeling efficiency at different copper: immunoconjugate ratios were used to determine the number of NOTA per antibody fragment molecule Supplementary Figure 5. PET imaging and biodistribution of 64CuCl2 in BXPC-3 tumor-bearing mice. Supplementary Figure 6. PET imaging and quantitative ROI analysis of 64Cu-NOTA-heterodimer with TF and CD105 dual-blocking in BXPC-3 tumor-bearing mice. Supplementary Figure 7. Coronal images and transverse PET/CT images of normal nude mice at 3, 15, 24 and 30 h following injection of 64Cu-NOTA-heterodimer Supplementary Figure 8. PET ROI-derived quantification of 64Cu-NOTA-heterodimer uptake in the tumor, normal pancreas, blood pool, liver, kidney and muscle at 3 h, 15 h, 24 h and 30 h p.i. of the tracer
- Published
- 2023
61. Supplementary Figure from Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein
- Author
-
Xiaoyuan Chen, Amir Kashefi, Lina He, Zibo Li, Weibo Cai, Kai Chen, and Hui Wang
- Abstract
Supplementary Figure from Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein
- Published
- 2023
62. Supplementary Figures S1-S2 from Integrin αvβ3-Targeted Radioimmunotherapy of Glioblastoma Multiforme
- Author
-
Xiaoyuan Chen, Fan Wang, Victor Tse, Andrew J. Connolly, Andrew R. Hsu, Cunjing Jin, Weibo Cai, Bing Jia, Kai Chen, Gang Niu, Zhaofei Liu, and Anand Veeravagu
- Abstract
Supplementary Figures S1-S2 from Integrin αvβ3-Targeted Radioimmunotherapy of Glioblastoma Multiforme
- Published
- 2023
63. Data from Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of Pancreatic Cancer
- Author
-
Weibo Cai, Robert J. Nickles, Hing C. Wong, Charles P. Theuer, Bai Liu, Reinier Hernandez, Stephen A. Graves, Sixiang Shi, Christopher G. England, and Haiming Luo
- Abstract
Purpose: Pancreatic adenocarcinoma is a highly aggressive cancer, currently treated with limited success and dismal outcomes. New diagnostic and treatment strategies offer the potential to reduce cancer mortality. Developing highly specific noninvasive imaging probes for pancreatic cancer is essential to improving diagnostic accuracy and monitoring therapeutic intervention.Experimental Design: A bispecific heterodimer was synthesized by conjugating an anti-tissue factor (TF) Fab with an anti-CD105 Fab, via the bio-orthogonal “click” reaction between tetrazine (Tz) and trans-cyclooctene (TCO). The heterodimer was labeled with 64Cu for PET imaging of nude mice bearing BXPC-3 xenograft and orthotopic pancreatic tumors.Results: PET imaging of BXPC-3 (TF/CD105+/+) xenograft tumors with 64Cu-labeled heterodimer displayed significantly enhanced tumor uptake (28.8 ± 3.2 %ID/g; n = 4; SD) at 30 hours postinjection, as compared with each of their monospecific Fab tracers (12.5 ± 1.4 and 7.1 ± 2.6 %ID/g; n = 3; SD). In addition, the activity–concentration ratio allowed for effective tumor visualization (tumor/muscle ratio 75.2 ± 9.4 at 30 hours postinjection.; n = 4; SD). Furthermore, 64Cu-NOTA-heterodimer enabled sensitive detection of orthotopic pancreatic tumor lesions with an uptake of 17.1 ± 4.9 %ID/g at 30 hours postinjection and tumor/muscle ratio of 72.3 ± 46.7.Conclusions: This study demonstrates that dual targeting of TF and CD105 provided synergistic improvements in binding affinity and tumor localization of the heterodimer. Dual-targeted imaging agents of pancreatic and other cancers may assist in diagnosing pancreatic malignancies as well as reliable monitoring of therapeutic response. Clin Cancer Res; 22(15); 3821–30. ©2016 AACR.
- Published
- 2023
64. Supplementary Figure 1 from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Author
-
Joseph C. Wu, Xiaoyuan Chen, Weibo Cai, Hui Wang, Kai Chen, Zhaofei Liu, Andrew Lee, Zibo Li, and Feng Cao
- Abstract
Supplementary Figure 1 from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Published
- 2023
65. Supplementary Methods and Figure Legend from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Author
-
Joseph C. Wu, Xiaoyuan Chen, Weibo Cai, Hui Wang, Kai Chen, Zhaofei Liu, Andrew Lee, Zibo Li, and Feng Cao
- Abstract
Supplementary Methods and Figure Legend from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Published
- 2023
66. Data from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Author
-
Joseph C. Wu, Xiaoyuan Chen, Weibo Cai, Hui Wang, Kai Chen, Zhaofei Liu, Andrew Lee, Zibo Li, and Feng Cao
- Abstract
Teratoma formation can be a serious drawback after the therapeutic transplantation of human embryonic stem (hES) cells. Therefore, noninvasive imaging of teratomas could be a valuable tool for monitoring patients undergoing hES cell treatment. Here, we investigated the angiogenic process within teratomas derived from hES cells and now report the first example of using 64Cu-labeled RGD tetramer (64Cu-DOTA-RGD4) for positron emission tomography imaging of teratoma formation by targeting αvβ3 integrin. H9 hES cells (2 × 106), stably expressing firefly luciferase, and enhanced green fluorescence protein (Fluc-eGFP) were injected into adult nude mice (n = 12) s.c. Eight weeks after transplantation, these hES cell grafts evolved into teratomas as confirmed by longitudinal bioluminescence imaging. Under micropositron emission tomography imaging, 2-deoxy-2-[18F]fluoro-D-glucose and 3′-deoxy-3′-[18F]-fluorothymidine both failed to detect hES cell–derived teratomas (0.8 ± 0.5 versus 1.1 ± 0.4 %ID/g, respectively; P = not significant versus background signals). By contrast, 64Cu-DOTA-RGD4 revealed specific and prominent uptake in vascularized teratoma and significantly lower uptake in control tumors (human ovarian carcinoma 2008 cell line), which had low intergrin expression (10.1 ± 3.4 versus 1.4 ± 1.2 %ID/g; P < 0.01). Immunofluorescence staining of CD31 and β3 integrin also supported our in vivo imaging results (P < 0.05). Moreover, we found that the cells dissociated from teratomas showed higher αvβ3 integrin expression than the 2008 cells. In conclusion, by targeting αvβ3 integrin, we successfully showed the ability of 64Cu-DOTA-RGD4 to noninvasively visualize teratoma formation in vivo for the first time. [Cancer Res 2009;69(7):2709–13]
- Published
- 2023
67. PD-L1 − targeted magnetic fluorescent hybrid nanoparticles: Illuminating the path of image-guided cancer immunotherapy
- Author
-
Xiaoyan Li, Muhsin H. Younis, Weijun Wei, and Weibo Cai
- Subjects
Radiology, Nuclear Medicine and imaging ,General Medicine - Published
- 2023
68. Radionuclide-based theranostics — a promising strategy for lung cancer
- Author
-
Tianxing Zhu, Jessica C. Hsu, Jingpei Guo, Weiyu Chen, Weibo Cai, and Kai Wang
- Subjects
Radiology, Nuclear Medicine and imaging ,General Medicine - Published
- 2023
69. Antibody-Based Imaging and Therapy for Precision Medicine
- Author
-
Weijun Wei, Dawei Jiang, Laura Evangelista, and Weibo Cai
- Subjects
Diagnostic Imaging ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Molecular Targeted Therapy ,Precision Medicine ,Antibodies - Published
- 2022
70. Recent biomedical advances enabled by HaloTag technology
- Author
-
WEIYU CHEN, MUHSIN H. YOUNIS, ZHONGKUO ZHAO, and WEIBO CAI
- Subjects
General Medicine - Abstract
The knowledge of interactions among functional proteins helps researchers understand disease mechanisms and design potential strategies for treatment. As a general approach, the fluorescent and affinity tags were employed for exploring this field by labeling the Protein of Interest (POI). However, the autofluorescence and weak binding strength significantly reduce the accuracy and specificity of these tags. Conversely, HaloTag, a novel self-labeling enzyme (SLE) tag, could quickly form a covalent bond with its ligand, enabling fast and specific labeling of POI. These desirable features greatly increase the accuracy and specificity, making the HaloTag a valuable system for various applications ranging from imaging to immobilization of POI. Notably, the HaloTag technique has already been successfully employed in a series of studies with excellent efficiency. In this review, we summarize the development of HaloTag and recent advanced investigations associated with HaloTag, including
- Published
- 2022
71. DNMT3B-mediated FAM111B methylation promotes papillary thyroid tumor glycolysis, growth and metastasis
- Author
-
Xiang, Zhu, Chunyuan, Xue, Xiaofeng, Kang, Xiaomeng, Jia, Lin, Wang, Muhsin H, Younis, Donghui, Liu, Nan, Huo, Yuchen, Han, Zhao, Chen, Jing, Fu, Chunyu, Zhou, Xiaoxiang, Yao, Yimeng, Du, Weibo, Cai, Lei, Kang, and Zhaohui, Lyu
- Subjects
Cell Cycle Proteins ,Estrogens ,Cell Biology ,Methylation ,Applied Microbiology and Biotechnology ,Gene Expression Regulation, Neoplastic ,Cell Movement ,Thyroid Cancer, Papillary ,Cell Line, Tumor ,Humans ,DNA (Cytosine-5-)-Methyltransferases ,Thyroid Neoplasms ,Glycolysis ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Cell Proliferation ,Developmental Biology - Abstract
Over the past decades, the incidence of thyroid cancer (TC) rapidly increased all over the world, with the papillary thyroid cancer (PTC) accounting for the vast majority of TC cases. It is crucial to investigate novel diagnostic and therapeutic targets for PTC and explore more detailed molecular mechanisms in the carcinogenesis and progression of PTC. Based on the TCGA and GEO databases, FAM111B is downregulated in PTC tissues and predicts better prognosis in PTC patients. FAM111B suppresses the growth, migration, invasion and glycolysis of PTC both
- Published
- 2022
72. Line Segment Matching Fusing Local Gradient Order and Non-Local Structure Information
- Author
-
Weibo Cai, Jintao Cheng, Juncan Deng, Yubin Zhou, Hua Xiao, Jian Zhang, and Kaiqing Luo
- Subjects
Fluid Flow and Transfer Processes ,Technology ,line segment matching ,QH301-705.5 ,Process Chemistry and Technology ,Physics ,QC1-999 ,General Engineering ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,non-local structure information ,gradient order ,Engineering (General). Civil engineering (General) ,Computer Science Applications ,Chemistry ,line feature ,General Materials Science ,TA1-2040 ,Biology (General) ,Instrumentation ,QD1-999 - Abstract
Line segment matching is essential for industrial applications such as scene reconstruction, pattern recognition, and VSLAM. To achieve good performance under the scene with illumination changes, we propose a line segment matching method fusing local gradient order and non-local structure information. This method begins with intensity histogram multiple averaging being utilized for adaptive partitioning. After that, the line support region is divided into several sub-regions, and the whole image is divided into a few intervals. Then the sub-regions are encoded by local gradient order, and the intervals are encoded by non-local structure information of the relationship between the sampled points and the anchor points. Finally, two histograms of the encoded vectors are, respectively, normalized and cascaded. The proposed method was tested on the public datasets and compared with previous methods, which are the line-junction-line (LJL), the mean-standard deviation line descriptor (MSLD) and the line-point invariant (LPI). Experiments show that our approach has better performance than the representative methods in various scenes. Therefore, a tentative conclusion can be drawn that this method is robust and suitable for various illumination changes scenes.
- Published
- 2022
73. ImmunoPET of trophoblast cell-surface antigen 2 (Trop-2) expression in pancreatic cancer
- Author
-
Joshua M Lang, Tuan-Wei Sun, Muhsin H Younis, Min Zhou, Todd E. Barnhart, Miao Li, Weibo Cai, Jonathan W. Engle, Dawei Jiang, and Weiyu Chen
- Subjects
endocrine system diseases ,Mice, Nude ,Article ,Flow cytometry ,Mice ,Antigen ,In vivo ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Survival rate ,medicine.diagnostic_test ,biology ,Cell growth ,business.industry ,Trophoblast ,General Medicine ,medicine.disease ,Trophoblasts ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Positron-Emission Tomography ,Antigens, Surface ,biology.protein ,Cancer research ,Zirconium ,Antibody ,business - Abstract
PURPOSE: Without a standard test for pancreatic carcinomas, this highly lethal disease is normally diagnosed at its advanced stage, leading to a low survival rate of patients. Trophoblast cell-surface antigen 2 (Trop-2), a transmembrane glycoprotein, is associated with cell proliferation and highly expressed in most of solid epithelial tumors, including pancreatic cancer. A non-invasive method of imaging Trop-2 would greatly benefit clinical diagnosis and monitoring of pancreatic cancer. In the current study, (89)Zr-labeled anti-Trop-2 antibody (AF650) was recruited for the systemic evaluation of Trop-2 as an immunoPET target for pancreatic cancer imaging. METHODS: AF650 was conjugated with desferrioxamine (DFO) and then radiolabeled with (89)Zr. Trop-2 expression levels were determined in three pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, and AsPC-1) via western blot, flow cytometry, saturation binding assay, and immunofluorescence staining. The targeting capacity of (89)Zr-DFO-AF650 was evaluated in mouse models with subcutaneous xenograft of pancreatic cancers via PET imaging and bio-distribution studies. In addition, a Trop-2-positive orthotopic cancer model was recruited for further validating the targeting specificity of (89)Zr-DFO-AF650. RESULTS: BxPC-3 cells expressed high levels of Trop-2, while AsPC-1 and MIA PaCa-2 cells expressed low levels of Trop-2. Additionally, (89)Zr-DFO-AF650 exhibited high specificity to Trop-2 in BxPC-3 cells (K(d) = 22.34 ± 2.509 nM). In subcutaneous xenograft models, about 28.8 ± 7.63%ID/g tracer accumulated in the BxPC-3 tumors at 120 h post injection, which was much higher than those reaching MIA PaCa-2 (6.76 ± 2.08%ID/g) and AsPC-1 (3.51 ± 0.69%ID/g) tumors (n = 4). More importantly, (89)Zr-DFO-AF650 could efficiently distinguish primary tumors in the orthotopic BxPC-3 cancer model, showing high correlation between PET imaging and bio-distribution and sensitivity. CONCLUSIONS: (89)Zr-DFO-AF650 can be effectively used to detect pancreatic cancer via Trop-2-mediated immunoPET in vivo, clearly revealing the great potential of Trop-2-based non-invasive imaging in pancreatic cancer detection and treatment monitoring.
- Published
- 2021
74. Vector enabled CRISPR gene editing – A revolutionary strategy for targeting the diversity of brain pathologies
- Author
-
Helen Forgham, Liwei Liu, Jiayuan Zhu, Ibrahim Javed, Weibo Cai, Ruirui Qiao, and Thomas P. Davis
- Subjects
Inorganic Chemistry ,Materials Chemistry ,Physical and Theoretical Chemistry - Published
- 2023
75. Wafer-scale heterostructured piezoelectric bio-organic thin films
- Author
-
Yutao Dong, Yizhan Wang, Dalong Ni, Jun Li, Timothy A. Hacker, Jiajie Sui, Fan Yang, Weibo Cai, Ping Wang, Ziyi Zhang, Xudong Wang, Rachel M Taylor, Yin Long, and Linfeng Wang
- Subjects
Materials science ,Cell Survival ,Glycine ,Biocompatible Materials ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Rats, Sprague-Dawley ,Stress (mechanics) ,Electricity ,Phase (matter) ,Animals ,Humans ,Wafer ,Thin film ,Cells, Cultured ,Density Functional Theory ,Multidisciplinary ,business.industry ,Biomaterial ,Hydrogen Bonding ,Prostheses and Implants ,021001 nanoscience & nanotechnology ,Piezoelectricity ,Elasticity ,Rats ,0104 chemical sciences ,Polyvinyl Alcohol ,Optoelectronics ,Stress, Mechanical ,Crystallization ,0210 nano-technology ,business ,Layer (electronics) ,Order of magnitude - Abstract
Piezoelectric bioorganic thin films Piezoelectric materials enable a reversible conversion between mechanical pressure and electric charge and are useful for sensors, actuators, and high-precision motors. Yang et al. developed a method for making high-quality crystalline thin films of piezoelectric γ-glycine crystals that are grown and refined between layers of polyvinyl alcohol (PVA) (see the Perspective by Berger). The PVA layers are essential to promoting the crystallization of the preferred crystal phase with the polar axis oriented perpendicular to the film plan because of hydrogen bonding at the PVA-glycine interface. The thin films show a macroscopic piezoelectric response and high stability in aqueous environments. The films are water soluble and, when suitably packaged, could be implanted into a biodegradable energy-harvesting device. Science , abf2155, this issue p. 337 ; see also abj0424, p. 278
- Published
- 2021
76. Ultrasmall Porous Silica Nanoparticles with Enhanced Pharmacokinetics for Cancer Theranostics
- Author
-
Carolina A. Ferreira, Shreya Goel, Tuan-Wei Sun, Eduardo Aluicio-Sarduy, Zachary T. Rosenkrans, Emily B. Ehlerding, Dalong Ni, Dawei Jiang, Weibo Cai, and Jonathan W. Engle
- Subjects
medicine.medical_treatment ,Bioengineering ,02 engineering and technology ,Article ,Silica nanoparticles ,Pharmacokinetics ,In vivo ,Cell Line, Tumor ,Neoplasms ,medicine ,Humans ,General Materials Science ,Precision Medicine ,business.industry ,Chemistry ,Mechanical Engineering ,Cancer ,General Chemistry ,Pet imaging ,Silicon Dioxide ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Radiation therapy ,Cancer management ,Cancer research ,Nanoparticles ,Personalized medicine ,0210 nano-technology ,business ,Porosity - Abstract
Theranostic nanoparticles hold the potential to greatly improve cancer management by providing personalized medicine. Although many theranostic nanoconstructs have been successful in preclinical studies, clinical translation is still hampered by their limited targeting capability and lack of successful therapeutic efficacy. We report the use of novel ultrasmall porous silica nanoparticles (UPSN) with enhanced in vivo pharmacokinetics such as high target tissue accumulation (12% ID/g in the tumor) and evasion from the reticuloendothelial system (RES) organs. Herein, UPSN is conjugated with the isotopic pair (90/86)Y, enabling both noninvasive imaging as well as internal radiotherapy. In vivo PET imaging demonstrates prolonged blood circulation and excellent tumor contrast with (86)Y-DOTA-UPSN. Tumor-to-muscle and tumor-to-liver uptake values were significantly high (12.4 ± 1.7 and 1.5 ± 0.5, respectively), unprecedented for inorganic nanomaterials. (90)Y-DOTA-UPSN significantly inhibits tumor growth and increases overall survival, indicating the promise of UPSN for future clinical translation as a cancer theranostic agent.
- Published
- 2021
77. ImmunoPET of CD38 with a radiolabeled nanobody: promising for clinical translation
- Author
-
Weibo Cai, Sixiang Shi, Xiaoli Lan, and Shreya Goel
- Subjects
medicine.medical_specialty ,Extramural ,business.industry ,MEDLINE ,Translation (biology) ,General Medicine ,Single-Domain Antibodies ,ADP-ribosyl Cyclase 1 ,Article ,Cell Line, Tumor ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical physics ,business - Published
- 2021
78. Open-shell nanosensitizers for glutathione-responsive sonodynamic therapy of breast cancer
- Author
-
Dalong Ni, Jonathan Engle, and Weibo Cai
- Subjects
Cancer Research ,Molecular Medicine ,Radiology, Nuclear Medicine and imaging - Published
- 2022
79. Spleen-Targeted Glabridin-Loaded Nanoparticles Regulate Polarization of Monocyte/Macrophage (M
- Author
-
Shiyong, Li, Ye, Wang, Miaojin, Wu, Muhsin H, Younis, Aeli P, Olson, Todd E, Barnhart, Jonathan W, Engle, Xingen, Zhu, and Weibo, Cai
- Subjects
Mice ,Phenols ,Macrophages ,Reperfusion Injury ,Animals ,Nanoparticles ,Isoflavones ,Monocytes ,Spleen - Abstract
During cerebral ischemia-reperfusion (I-R) injury, the infiltration of monocyte/macrophages (M
- Published
- 2022
80. Engineering CpG-ASO-Pt-Loaded Macrophages (CAP@M) for Synergistic Chemo-/Gene-/Immuno-Therapy
- Author
-
Yuqi Wang, Lingpu Zhang, Yan Liu, Linlin Tang, Juan He, Xiaqing Sun, Muhsin H. Younis, Daxiang Cui, Haihua Xiao, Dong Gao, Xiang‐Yang Kong, Weibo Cai, and Jie Song
- Subjects
Biomaterials ,Drug Delivery Systems ,Nanomedicine ,Cell Line, Tumor ,Macrophages ,Biomedical Engineering ,Pharmaceutical Science ,Nanoparticles ,Antineoplastic Agents ,Nanospheres - Abstract
Adoptive cell therapy by natural cells for drug delivery has achieved encouraging progress in cancer treatment over small-molecule drugs. Macrophages have a great potential in antitumor drug delivery due to their innate capability of sensing chemotactic cues and homing toward tumors. However, major challenge in current macrophage-based cell therapy is loading macrophages with adequate amounts of therapeutic, while allowing them to play a role in immunity without compromising cell functions. Herein, a potent strategy to construct a macrophage-mediated drug delivery platform loaded with a nanosphere (CpG-ASO-Pt) (CAP) composed of functional nucleic acid therapeutic (CpG-ASO) and chemotherapeutic drug cisplatin (Pt) is demonstrated. These CAP nanosphere loaded macrophages (CAP@M) are employed not only as carriers to deliver this nanosphere toward the tumor sites, but also simultaneously to guide the differentiation and maintain immunostimulatory effects. Both in vitro and in vivo experiments indicate that CAP@M is a promising nanomedicine by macrophage-mediated nanospheres delivery and synergistically immunostimulatory activities. Taken together, this study provides a new strategy to construct a macrophage-based drug delivery system for synergistic chemo-/gene-/immuno-therapy.
- Published
- 2022
81. Multimodality imaging of <scp>nanoparticle‐based</scp> vaccines: Shedding light on immunology
- Author
-
Muhsin H. Younis, Zhongmin Tang, and Weibo Cai
- Subjects
Tomography, Emission-Computed, Single-Photon ,Vaccines ,Nanomedicine ,Positron-Emission Tomography ,Biomedical Engineering ,Nanoparticles ,Medicine (miscellaneous) ,Bioengineering ,Magnetic Resonance Imaging - Abstract
In recent years, there have been significant innovations in the development of nanoparticle-based vaccines and vaccine delivery systems. For the purposes of both design and evaluation, these nanovaccines are imaged using the wealth of understanding established around medical imaging of nanomaterials. An important insight to the advancement of the field of nanovaccines can be given by an analysis of the design rationale of an imaging platform, as well as the significance of the information provided by imaging. Nanovaccine imaging strategies can be categorized by the imaging modality leveraged, but it is also worth understanding the superiority or convenience of a given modality over others in a given context of a particular nanovaccine. The most important imaging modalities in this endeavor are optical imaging including near-infrared fluorescence imaging (NIRF), emission tomography methods such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) with or without computed tomography (CT) or magnetic resonance (MR), the emerging magnetic particle imaging (MPI), and finally, multimodal applications of imaging which include molecular imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. One finds that each of these modalities has strengths and weaknesses, but optical and PET imaging tend, in this context, to be currently the most accessible, convenient, and informative modalities. Nevertheless, an important principle is that there is not a one-size-fits-all solution, and that the specific nanovaccine in question must be compatible with a particular imaging modality. This article is categorized under: Nanotechnology Approaches to BiologyNanoscale Systems in Biology Therapeutic Approaches and Drug DiscoveryNanomedicine for Oncologic Disease Therapeutic Approaches and Drug DiscoveryNanomedicine for Infectious Disease.
- Published
- 2022
82. Enhancing fibroblast activation protein (FAP)-targeted radionuclide therapy with albumin binding, and beyond
- Author
-
Muhsin H. Younis, Sara Malih, Xiaoli Lan, Mohammad Javad Rasaee, and Weibo Cai
- Subjects
Radioisotopes ,Gelatinases ,Albumins ,Serine Endopeptidases ,Humans ,Radiology, Nuclear Medicine and imaging ,General Medicine ,Fibroblasts ,Article - Published
- 2022
83. PET Imaging of Tumor Integrin Expression.
- Author
-
Weibo Cai and Xiaoyuan Chen
- Published
- 2005
- Full Text
- View/download PDF
84. Antioxidant and C5a-blocking strategy for hepatic ischemia–reperfusion injury repair
- Author
-
Weibo Cai, Dong Wu, Jonathan W. Engle, Jiajia Hu, Shuping Qu, Kaelyn V Becker, Xiaobing Zhang, and Dalong Ni
- Subjects
Antioxidant ,medicine.medical_treatment ,Pharmaceutical Science ,Medicine (miscellaneous) ,02 engineering and technology ,Pharmacology ,medicine.disease_cause ,01 natural sciences ,Applied Microbiology and Biotechnology ,Antioxidants ,Mice ,Ischemia ,Medicine ,chemistry.chemical_classification ,Cerium ,021001 nanoscience & nanotechnology ,Hepatic ischemia ,Nanomedicine ,Hepatic ischemia–reperfusion injury ,Nanoceria ,Liver ,Reperfusion Injury ,Cytokines ,Molecular Medicine ,Female ,Inflammation Mediators ,medicine.symptom ,0210 nano-technology ,Biotechnology ,C5a ,Aptamer ,Biomedical Engineering ,Complement C5a ,Bioengineering ,Inflammation ,010402 general chemistry ,Medical technology ,Animals ,Distribution (pharmacology) ,R855-855.5 ,Reactive oxygen species ,business.industry ,Research ,medicine.disease ,Molecular medicine ,0104 chemical sciences ,Disease Models, Animal ,Oxidative Stress ,Nanoantioxidants ,RAW 264.7 Cells ,chemistry ,Reactive Oxygen Species ,business ,Reperfusion injury ,Oxidative stress ,TP248.13-248.65 - Abstract
Background Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials’ propensity for liver distribution might enable their use in hepatic ischemia–reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair. Results To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited. Conclusions The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases. Graphic abstract
- Published
- 2021
85. ImmunoPET/NIRF/Cerenkov multimodality imaging of ICAM-1 in pancreatic ductal adenocarcinoma
- Author
-
Kevin Fan, Dawei Jiang, Weiyu Chen, Weijun Wei, Jianjun Liu, Weibo Cai, Jonathan W. Engle, Todd E. Barnhart, Miao Li, and Tianye Cao
- Subjects
Biodistribution ,endocrine system diseases ,medicine.drug_class ,Mice, Nude ,Monoclonal antibody ,Article ,030218 nuclear medicine & medical imaging ,Flow cytometry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,ICAM-1 ,medicine.diagnostic_test ,business.industry ,General Medicine ,Intercellular Adhesion Molecule-1 ,Isotype ,digestive system diseases ,Pancreatic Neoplasms ,Cell culture ,Positron emission tomography ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Cancer research ,Zirconium ,business ,Carcinoma, Pancreatic Ductal - Abstract
PURPOSE: We dual-labeled an intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody (mAb) and evaluated its effectiveness for lesion detection and surgical navigation in pancreatic ductal adenocarcinoma (PDAC) via multiple noninvasive imaging approaches, including positron emission tomography (PET), near-infrared fluorescence (NIRF), and Cerenkov luminescence imaging (CLI). METHODS: ICAM-1 expression in PDAC cell lines (BxPC-3 and AsPC-1) was assessed via flow cytometry and immunofluorescent staining. An ICAM-1 mAb labeled by IRDye 800CW and radionuclide zirconium-89 (denoted as [(89)Zr]Zr-DFO-ICAM-1-IR800) was synthesized. Its performance was validated via in vivo comparative PET/NIRF/CLI and biodistribution (Bio-D) studies in nude mice bearing subcutaneous BxPC-3/AsPC-1 tumors or orthotopic BxPC-3 tumor models using nonspecific IgG as an isotype control tracer. RESULTS: ICAM-1 expression was strong in the BxPC-3 and minimal in the AsPC-1 cell line. Both multimodality imaging and Bio-D data exhibited more prominent uptake of [(89)Zr]Zr-DFO-ICAM-1-IR800 in BxPC-3 tumors than in AsPC-1 tumors. The uptake of [(89)Zr]Zr-DFO-IgG-IR800 in BxPC-3 tumors was similar to that of [(89)Zr]Zr-DFO-ICAM-1-IR800 in AsPC-1 tumors. These results demonstrate the desirable affinity and specificity of [(89)Zr]Zr-DFO-ICAM-1-IR800 compared to [(89)Zr]Zr-DFO-IgG-IR800. Orthotopic BxPC-3 tumor foci could also be clearly delineated by [(89)Zr]Zr-DFO-ICAM-1-IR800. An intermodal match was achieved in the ICAM-1-targeted immunoPET/NIRF/CLI. The positive expression levels of ICAM-1 in BxPC-3 tumor tissue were further confirmed by immunohistopathology. CONCLUSION: We successfully developed a dual-labeled ICAM-1-targeted tracer for PET/NIRF/CLI of PDAC that can facilitate better diagnosis and intervention of PDAC upon clinical translation.
- Published
- 2021
86. High-performance renal imaging with a radiolabeled, non-excretable chimeric fusion protein
- Author
-
Muhsin H Younis, Weibo Cai, Xiaoli Lan, and Dawei Jiang
- Subjects
Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,Recombinant Fusion Proteins ,Medicine (miscellaneous) ,Renal function ,Receptors, Fc ,single photon emission computed tomography (SPECT) ,Kidney ,Renal scintigraphy ,vascular endothelial growth factor (VEGF) ,renal scan ,Neonatal Fc receptor ,polybasic tag (PBT) ,Medicine ,Animals ,Humans ,nuclear medicine ,Tubular basement membrane ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Radioisotopes ,Tomography, Emission-Computed, Single-Photon ,neonatal Fc receptor ,business.industry ,Histocompatibility Antigens Class I ,Technetium ,Biological Transport ,Fusion protein ,Kidney imaging ,Tc-99m ,Renal imaging ,Editorial ,Renal physiology ,Radiopharmaceuticals ,business ,Tomography, X-Ray Computed ,recombinant protein - Abstract
Ideal nuclear imaging tracers should exhibit high target uptake and low background signal. Traditional renal scintigraphy and SPECT scans examine kidney function via static or dynamic tracing of radioactive probes in the kidneys. The lack of tracer affinity to specific biological processes and high background uptake from urinary excretion have added many difficulties to precision renal diagnosis. In this issue of Theranostics, Jin and colleagues innovatively devised a recombinant probe for preferential kidney imaging through targeting of tubular neonatal Fc receptor and proximal tubular basement membrane for sustained tubular reabsorption and accumulation. This work has broad implications regarding how an in depth understanding of physiology and pathology may be of service for tracer development, renal diagnosis, and disease theranostics.
- Published
- 2021
87. Dynamic PET imaging with ultra-low-activity of 18F-FDG: unleashing the potential of total-body PET
- Author
-
Kevin Fan, Ke Li, Weibo Cai, and Xiaoli Lan
- Subjects
business.industry ,Low activity ,Medicine ,Radiology, Nuclear Medicine and imaging ,Total body ,General Medicine ,Pet imaging ,business ,Nuclear medicine - Published
- 2021
88. Single-Domain Antibody Theranostics on the Horizon
- Author
-
Weijun Wei, Muhsin H. Younis, Xiaoli Lan, Jianjun Liu, and Weibo Cai
- Subjects
Humans ,Radiology, Nuclear Medicine and imaging ,Precision Medicine ,Single-Domain Antibodies ,B7-H1 Antigen ,Molecular Imaging ,Focus on Molecular Imaging - Abstract
Single-domain antibody (sdAb) is among the most promising vectors for developing molecular imaging tracers. Several sdAb tracers targeting human epidermal growth factor receptor 2 or programmed death ligand 1 have entered clinical practice. However, radiolabeled single-valent sdAbs generally have high kidney retention, limiting their therapeutic applications. Therefore, engineering strategies such as PEGylation or incorporation of renal cleavable linkers can be adapted to improve pharmacokinetics and reduce kidney retention. In this Focus on Molecular Imaging review, we try to summarize the latest developments in sdAb-derived agents and propose potential strategies that can be used to improve the theranostic value of radiolabeled sdAbs.
- Published
- 2022
89. Open-Shell Nanosensitizers for Glutathione Responsive Cancer Sonodynamic Therapy
- Author
-
Han Wang, Jinxiao Guo, Wilson Lin, Zi Fu, Xiuru Ji, Bo Yu, Min Lu, Wenguo Cui, Lianfu Deng, Jonathan W. Engle, Zhiyuan Wu, Weibo Cai, and Dalong Ni
- Subjects
Porphyrins ,Mechanics of Materials ,Mechanical Engineering ,Cell Line, Tumor ,Neoplasms ,Ultrasonic Therapy ,Humans ,General Materials Science ,Glutathione ,Article ,Polyethylene Glycols - Abstract
Deleterious effects to normal tissues and short biological half-life of sonosensitizers limit the applications of sonodynamic therapy (SDT). Herein we synthesize a new sonosensitizer (Cu(II)NS) that consists of porphyrins, the chelated Cu(2+), and PEG to overcome the challenges of SDT. As Cu(2+) contains 27 electrons, Cu(II)NS have an unpaired electron (open shell), resulting in a doublet ground state and little sonosensitivity. Overexpressed glutathione (GSH) in the tumor can reduce Cu(2+) to generate Cu(I)NS, leading to a singlet ground state and recuperative sonosensitivity. Additionally, PEG endows Cu(II)NS with increased blood biological half-life and enhanced tumor accumulation, further increasing the effect of SDT. Through regulating the valence state of Cu, we achieve cancer SDT with enhanced therapeutic index.
- Published
- 2022
90. Front Cover: Spherical nucleic acids: Organized nucleotide aggregates as versatile nanomedicine
- Author
-
Yangmeihui Song, Wenyu Song, Xiaoli Lan, Weibo Cai, and Dawei Jiang
- Subjects
General Medicine - Published
- 2022
91. Prevention of Hepatic Ischemia-Reperfusion Injury by Carbohydrate-Derived Nanoantioxidants
- Author
-
Dawei Jiang, Tuan-Wei Sun, Jun Li, Weibo Cai, Hao Wei, Lazarus G German, Jonathan W. Engle, Xudong Wang, Ziyi Zhang, Corey Carlos, Yin Long, Tianye Cao, Yadong Jiang, Xiaoli Lan, Mengting Li, and Yizhan Wang
- Subjects
Carbohydrates ,chemistry.chemical_element ,Bioengineering ,02 engineering and technology ,Pharmacology ,Oxygen ,Article ,Ros scavenging ,medicine ,Animals ,General Materials Science ,chemistry.chemical_classification ,Reactive oxygen species ,Chemistry ,Mechanical Engineering ,General Chemistry ,Surgical procedures ,Carbohydrate ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Hepatic ischemia ,Liver ,Reperfusion Injury ,Nanoparticles ,Liver dysfunction ,Reactive Oxygen Species ,0210 nano-technology ,Reperfusion injury - Abstract
Hepatic ischemia-reperfusion injury (IRI), which mainly results from excessive reactive oxygen species (ROS) generated by a reperfusion burst of oxygen, has long been a major cause of liver dysfunction and failure after surgical procedures. Here, a monodispersed hydrophilic carbohydrate-derived nanoparticle (C-NP) was synthesized as a nanoantioxidant that could effectively prevent hepatic IRI. The spherical C-NPs had a size of ∼78 ± 11.3 nm covered with polar surface groups. They were well dispersible in water with good colloidal stability, nontoxicity, and good ROS scavenging capability. The C-NPs also exhibited good circulation lifetime, effective delivery to liver, and gradual degradability with an ability to assist the IRI group maintaining a normal and healthy liver status. The pathology mechanism of C-NPs in hepatic IRI was confirmed to be scavenging of excessive ROS by C-NPs. The effective therapeutic treatment of C-NPs in living animals revealed a great potential in clinical prevention for hepatic IRI.
- Published
- 2020
92. Nanomedicines for Renal Management: From Imaging to Treatment
- Author
-
Dalong Ni, Zachary T. Rosenkrans, Peng Huang, Weibo Cai, Dawei Jiang, and Jing Lin
- Subjects
Contrast Media ,Metal Nanoparticles ,Biocompatible Materials ,Nanotechnology ,Kidney ,010402 general chemistry ,Renal care ,01 natural sciences ,Article ,Biological property ,medicine ,Animals ,Glucocorticoids ,010405 organic chemistry ,DNA ,General Medicine ,General Chemistry ,Biocompatible material ,Magnetic Resonance Imaging ,Nanostructures ,0104 chemical sciences ,Nanomedicine ,medicine.anatomical_structure ,Carbon quantum dots ,Positron-Emission Tomography ,Kidney Diseases ,Gold ,Tomography, X-Ray Computed ,Glomerular Filtration Rate ,Clearance ,Potential toxicity - Abstract
Nanomedicine has benefited from recent advances in chemistry and biomedical engineering to produce nanoscale materials as theranostic agents. Well-designed nanomaterials may present optimal biological properties, influencing circulation, retention, and excretion for imaging and treatment of various diseases. As the understanding of nanomedicine pharmacokinetics expands continuously, efficient renal clearance of nanomedicines can significantly increase the signal-to-background ratio for precision diagnosis and lower potential toxicity for improved treatment. Studies on nanomaterial-kidney interactions have led to many novel findings on the underlying principles of nanomaterial renal clearance, targeting, and accumulation. In return, the optimized nanomedicines confer significant benefits to the detection and treatment of kidney dysfunction.In this Account, we present an overview of recent progress in the development of nanomaterials for kidney theranostics, aiming to speed up translation and expand possible applications. We start by introducing biological structures of the kidney and their influence on renal targeting, retention, and clearance. Several key factors regarding renal accumulation and excretion, including nanomaterial types, sizes, and shapes, surface charges, and chemical modifications, are identified and discussed. Next, we highlight our recent efforts investigating kidney-interacting nanomaterials and introduce representative nanomedicines for imaging and treatment of kidney diseases. Multiple renal-clearable and renal-accumulating nanomedicines were devised for kidney function imaging. By employing renal-clearable nanomedicines, including gold nanoparticles, porphyrin polymers, DNA frameworks, and polyoxometalate clusters, we were able to noninvasively evaluate split renal function in healthy and diseased mice. Further engineering of renal-accumulating nanosystems has shifted attention from renal diagnosis to precision kidney protection. Many biocompatible nanomedicines, such as DNA origami, selenium-doped carbon quantum dots, melanin nanoparticles, and black phosphorus have all played essential roles in diminishing excessive reactive oxygen species for kidney treatment and protection. Finally, we discuss the challenges and perspectives of nanomaterials for renal care, their future clinical translation, and how they may affect the current landscape of clinical practices. We believe that this Account updates our current understanding of nanomaterial-kidney interactions for further design and control of nanomedicines for specific kidney diagnosis and treatment. This timely Account will generate broad interest in integrating nanotechnology and nanomaterial-biological interaction for state-of-the-art theranostics of renal diseases.
- Published
- 2020
93. Development and characterization of CD54-targeted immunoPET imaging in solid tumors
- Author
-
Hye Jin Lee, Weibo Cai, Jonathan W. Engle, Christopher J. Kutyreff, Miao Li, Dawei Jiang, Jianjun Liu, and Weijun Wei
- Subjects
Biodistribution ,medicine.drug_class ,Monoclonal antibody ,Article ,030218 nuclear medicine & medical imaging ,Flow cytometry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,Thyroid Neoplasms ,Anaplastic thyroid cancer ,Thyroid cancer ,biology ,medicine.diagnostic_test ,business.industry ,Melanoma ,Antibodies, Monoclonal ,General Medicine ,Intercellular Adhesion Molecule-1 ,medicine.disease ,Cell culture ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Antibody ,business - Abstract
PURPOSE: Intercellular adhesion molecule-1 (ICAM-1, CD54) is an emerging therapeutic target for a variety of solid tumors including melanoma and anaplastic thyroid cancer (ATC). This study aims to develop an ICAM-1-targeted immuno-positron emission tomography (immunoPET) imaging strategy and assess its diagnostic value in melanoma and ATC models. METHODS: Flow cytometry was used to screen ICAM-1-positive melanoma and ATC cell lines. Melanoma and ATC models were established using A375 cell line and THJ-16T cell line, respectively. An ICAM-1-specific monoclonal antibody (R6–5-D6) and a nonspecific human IgG were radiolabeled with (64)Cu and the diagnostic efficacies were interrogated in tumor-bearing mouse models. Biodistribution and fluorescent imaging studies were performed to confirm the specificity of the ICAM-1-targeted imaging probes. RESULTS: ICAM-1 was strongly expressed on melanoma and advanced thyroid cancer cell lines. (64)Cu-NOTA-ICAM-1 immunoPET imaging efficiently delineated A375 melanomas with a peak tumor uptake of 21.28 ± 6.56 %ID/g (n = 5), significantly higher than that of (64)Cu-NOTA-IgG (10.63 ± 2.58 %ID/g, n = 3). Moreover, immunoPET imaging with (64)Cu-NOTA-ICAM-1 efficiently visualized subcutaneous and orthotopic ATCs with high clarity and contrast. Fluorescent imaging with IRDye 800CW-ICAM-1 also visualized orthotopic ATCs and the tumor uptake could be blocked by the ICAM-1 parental antibody R6–5-D6, indicating the high specificity of the developed probe. Finally, blocking with the human IgG prolonged the circulation of the (64)Cu-NOTA-ICAM-1 in R2G2 mice without compromising the tumor uptake. CONCLUSION: ICAM-1-targeted immunoPET imaging could characterize ICAM-1 expression in melanoma and ATC, which holds promise for optimizing ICAM-1-targeted therapies in the future.
- Published
- 2020
94. 86/90Y-Labeled Monoclonal Antibody Targeting Tissue Factor for Pancreatic Cancer Theranostics
- Author
-
Eduardo Aluicio-Sarduy, Tuan-Wei Sun, Zachary T. Rosenkrans, Emily B. Ehlerding, Weibo Cai, Jonathan W. Engle, Dalong Ni, Dawei Jiang, and Carolina A. Ferreira
- Subjects
Poor prognosis ,endocrine system diseases ,medicine.drug_class ,medicine.medical_treatment ,Pharmaceutical Science ,02 engineering and technology ,Monoclonal antibody ,030226 pharmacology & pharmacy ,Article ,03 medical and health sciences ,Tissue factor ,0302 clinical medicine ,Pancreatic cancer ,Drug Discovery ,Overall survival ,Medicine ,Paca ,biology ,business.industry ,021001 nanoscience & nanotechnology ,medicine.disease ,biology.organism_classification ,Radioimmunotherapy ,Cancer research ,Molecular Medicine ,0210 nano-technology ,business ,Median survival - Abstract
Pancreatic cancer is highly aggressive, with a median survival time of less than 6 months and a 5-year overall survival rate of around 7%. The poor prognosis of PaCa is largely due to its advanced stage at diagnosis and the lack of efficient therapeutic options. Thus, the development of an efficient, multifunctional PaCa theranostic system is urgently needed. Overexpression of tissue factor (TF) has been associated with increased tumor growth, angiogenesis, and metastasis in many malignancies, including pancreatic cancer. Herein, we propose the use of a TF-targeted monoclonal antibody (ALT836) conjugated with the pair (86/90)Y as atheranostic agent against pancreatic cancer. For methods, serial PET imaging with (86)Y-DTPA-ALT836 was conducted to map the biodistribution the tracer in BXPC-3 tumor-bearing mice. (90)Y-DTPA-ALT836 was employed as a therapeutic agent that also allowed tumor burden monitoring through Cherenkov luminescence imaging. The results were that the uptake of (86)Y-DTPA-ALT836 in BXPC-3 xenograft tumors was high and increased over time up to 48 h postinjection (p.i.), corroborated through ex vivo biodistribution studies and further confirmed by Cherenkov luminescence Imaging. In therapeutic studies, (90)Y-DTPA-ALT836 was found to slow tumor growth relative to the control groups and had significantly smaller (p < 0.05) tumor volumes 1 day p.i. Histological analysis of ex vivo tissues revealed significant damage to the treated tumors. The conclusion is that the use of the (86/90)Y theranostic pair allows PET imaging with excellent tumor-to-background contrast and treatment of TF-expressing pancreatic tumors with promising therapeutic outcomes.
- Published
- 2020
95. Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles
- Author
-
Yanyu Huang, Yuanting Fu, Mengting Li, Dawei Jiang, Christopher J. Kutyreff, Jonathan W. Engle, Xiaoli Lan, Weibo Cai, and Tianfeng Chen
- Subjects
General Medicine - Published
- 2020
96. Self‐Amplified Photodynamic Therapy through the 1 O 2 ‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer
- Author
-
Zhiyong Liu, Tianye Cao, Yudong Xue, Mengting Li, Mengsi Wu, Jonathan W. Engle, Qianjun He, Weibo Cai, Minbo Lan, and Weian Zhang
- Subjects
General Medicine - Published
- 2020
97. Self‐Amplified Photodynamic Therapy through the 1 O 2 ‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer
- Author
-
Weian Zhang, Tianye Cao, Mengting Li, Yudong Xue, Mengsi Wu, Weibo Cai, Jonathan W. Engle, Qianjun He, Minbo Lan, and Zhiyong Liu
- Subjects
chemistry.chemical_classification ,Reactive oxygen species ,010405 organic chemistry ,Chemistry ,Singlet oxygen ,medicine.medical_treatment ,media_common.quotation_subject ,Photodynamic therapy ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Drug delivery ,Cancer cell ,Copolymer ,medicine ,Biophysics ,Nanocarriers ,Internalization ,media_common - Abstract
Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non-selective release of photosensitizers still exist. Herein, we report a 1 O2 -responsive block copolymer (POEGMA-b-P(MAA-co-VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (1 O2 ) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1 O2 -responsiveness of POEGMA-b-P(MAA-co-VSPpaMA) block copolymer enabled the realization of self-amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.
- Published
- 2020
98. Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles
- Author
-
Mengting Li, Xiaoli Lan, Yanyu Huang, Dawei Jiang, Tianfeng Chen, Christopher J. Kutyreff, Weibo Cai, Jonathan W. Engle, and Yuanting Fu
- Subjects
inorganic chemicals ,Biodistribution ,Circular dichroism ,Antioxidant ,medicine.medical_treatment ,Kinetics ,Contrast Media ,chemistry.chemical_element ,Nanoparticle ,Apoptosis ,010402 general chemistry ,01 natural sciences ,Article ,Antioxidants ,Mass Spectrometry ,Catalysis ,Mice ,Selenium ,Cell Adhesion ,medicine ,Animals ,Humans ,Tissue Distribution ,010405 organic chemistry ,Chemistry ,technology, industry, and agriculture ,Biological Transport ,Stereoisomerism ,General Chemistry ,Glutathione ,Rats ,0104 chemical sciences ,Oxidative Stress ,Copper Radioisotopes ,Positron-Emission Tomography ,Biophysics ,Nanoparticles ,Enantiomer ,Chirality (chemistry) ,Oxidation-Reduction - Abstract
The chirality of nanoparticles directly influences their transport and biological effect under physiological environment, but the details of this phenomenon have rarely been explored. Herein, chiral GSH-anchored selenium nanoparticles (G@SeNPs) are fabricated to investigate the interaction between their chirality and transport and antioxidant activity. G@SeNPs modified with different enantiomers show opposite handedness with a tunable circular dichroism signal. The noninvasive positron emission tomography imaging clearly reveals that (64)Cu-labeled (L)-G@SeNPs experience distinctly different transport among the major organs from their (D)-and (DL)-counterparts, demonstrating that the chirality of the G@SeNPs influences the biodistribution and kinetics. Taking advantage of the strong homologous cell adhesion and uptake, (L)-G@SeNPs have been shown here to effectively prevent oxidation damage caused by palmitic acid in insulinoma cells. This work should motivate the biomedical applications of chiral nanomedicine by providing a fundamental understanding of chirality-dependent biodistribution and antioxidant activity.
- Published
- 2020
99. Clinical summary of fibroblast activation protein inhibitor-based radiopharmaceuticals: cancer and beyond
- Author
-
Mengting Li, Muhsin H. Younis, Yongxue Zhang, Weibo Cai, and Xiaoli Lan
- Subjects
Gelatinases ,Neoplasms ,Positron Emission Tomography Computed Tomography ,Serine Endopeptidases ,Humans ,Membrane Proteins ,Radiology, Nuclear Medicine and imaging ,General Medicine ,Fibroblasts ,Radiopharmaceuticals ,Article - Abstract
Fibroblast activation protein (FAP) is a type II membrane-bound glycoprotein which is overexpressed in cancer-associated fibroblasts and activated fibroblasts at wound healing/inflammatory sites. Since the first clinical application of quinoline-based FAP ligands in 2018, FAP inhibitor (FAPI)-based PET imaging and radiotherapy have been investigated for a wide variety of diseases, both cancerous and non-cancerous. As a consequence, promising strides have been made in particular to improve the understanding of FAPI-based PET imaging and the potential value of FAPI-based tumor radiotherapy. Herein, we present a comprehensive review of radiolabeled FAPI, including their clinical translation, in order to clarify the current and potential future role of this class of molecules in nuclear medicine. In particular, this review underlines the value of FAPI radiopharmaceuticals in the diagnosis or therapy of tumors or benign conditions. However, limitations in present studies have hampered a precise evaluation of FAPI radiopharmaceuticals. Despite this, it will likely be worthwhile to further explore the clinical value of FAPI in diagnosis and therapy through better-designed and larger-population clinical trials in the future.
- Published
- 2021
100. Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury
- Author
-
Hao Wei, Dawei Jiang, Bo Yu, Dalong Ni, Mengting Li, Yin Long, Paul A. Ellison, Cerise M. Siamof, Liang Cheng, Todd E. Barnhart, Hyung-Jun Im, Faquan Yu, Xiaoli Lan, Xiaohua Zhu, Qianjun He, and Weibo Cai
- Subjects
Biomaterials ,Biomedical Engineering ,Biotechnology - Abstract
Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles
- Published
- 2021
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.