{"title":"Advances in Tracing Techniques: Mapping the Trajectory of Mesenchymal Stem-Cell-Derived Extracellular Vesicles","authors":"Jingqi Li, Zhaoyu Wang, Yongchun Wei, Wenshuai Li, Mingzhu He, Jingjing Kang, Jia Xu and Dingbin Liu*, ","doi":"10.1021/cbmi.4c0008510.1021/cbmi.4c00085","DOIUrl":"https://doi.org/10.1021/cbmi.4c00085https://doi.org/10.1021/cbmi.4c00085","url":null,"abstract":"<p >Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are nanoscale lipid bilayer vesicles secreted by mesenchymal stem cells. They inherit the parent cell’s attributes, facilitating tissue repair and regeneration, promoting angiogenesis, and modulating the immune response, while offering advantages like reduced immunogenicity, straightforward administration, and enhanced stability for long-term storage. These characteristics elevate MSC-EVs as highly promising in cell-free therapy with notable clinical potential. It is critical to delve into their pharmacokinetics and thoroughly elucidate their intracellular and <i>in vivo</i> trajectories. A detailed summary and evaluation of existing tracing strategies are needed to establish standardized protocols. Here, we have summarized and anticipated the research progress of MSC-EVs in various biomedical imaging techniques, including fluorescence imaging, bioluminescence imaging, nuclear imaging (PET, SPECT), tomographic imaging (CT, MRI), and photoacoustic imaging. The challenges and prospects of MSC-EV tracing strategies, with particular emphasis on clinical translation, have been analyzed, with promising solutions proposed.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 3","pages":"137–168 137–168"},"PeriodicalIF":0.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determining the Multivalent Effects of d-Peptide-Based Radiotracers.","authors":"Siqi Zhang, Xiaona Sun, Wenhao Liu, Jiang Wu, Yuxuan Wu, Shuo Jiang, Xingkai Wang, Xin Gao, Quan Zuo, Hailong Zhang, Yingzi Zhang, Feng Wang, Rui Wang, Kuan Hu","doi":"10.1021/cbmi.4c00071","DOIUrl":"10.1021/cbmi.4c00071","url":null,"abstract":"<p><p>Dextrorotary (d) peptides, composed of d-amino acids, are hyper-resistant to proteolytic hydrolysis, making them valuable ligands with excellent <i>in vivo</i> stability for radiopharmaceutical development. Multimerization is a well-established strategy for enhancing the <i>in vivo</i> performance of l-peptide-based radiopharmaceuticals. However, the effect of multimerization on the <i>in vivo</i> fate of d-peptide-based radiopharmaceuticals remains largely unexplored. Here, we synthesized the d-peptide DPA, which targets PD-L1, along with its dimer (DP2) and trimer (DP3). PET/CT imaging and <i>ex vivo</i> biodistribution studies were performed to delineate the pharmacokinetics and target interactions of [<sup>68</sup>Ga]DPA, [<sup>68</sup>Ga]DP2, and [<sup>68</sup>Ga]DP3 in both normal and tumor-bearing mice. Our results revealed that tumor uptake and kidney retention increased with higher valency ([<sup>68</sup>Ga]DP3 > [<sup>68</sup>Ga]DP2 > [<sup>68</sup>Ga]DPA). No significant differences were observed in the liver, heart, lung, spleen, intestine, or bone among the three radiotracers. Interestingly, a significant reduction of radioactivity in the bloodstream was detected for the [<sup>68</sup>Ga]DP3-treated group compared to the other two groups. Data analysis revealed that chiral configuration of amino acids and the linking chemistry used in multimerization are the two dominant factors in the <i>in vivo</i> fate of d-peptide multimers. These findings indicate that d-peptide multimerization exerts a distinct influence on <i>in vivo</i> profiles compared to l-peptide multimerization. This study deepens our understanding of how mirror-imaged peptides/proteins interact with the living systems, paving the way for the development of radiopharmaceuticals that harness d-peptides as targeting moieties.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 3","pages":"180-190"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandrine Truchet, Jeanne Malet-Villemagne, Gilles Tessier and Jasmina Vidic*,
{"title":"Visualization of the Biogenesis, Dynamics, and Host Interactions of Bacterial Extracellular Vesicles","authors":"Sandrine Truchet, Jeanne Malet-Villemagne, Gilles Tessier and Jasmina Vidic*, ","doi":"10.1021/cbmi.5c0000210.1021/cbmi.5c00002","DOIUrl":"https://doi.org/10.1021/cbmi.5c00002https://doi.org/10.1021/cbmi.5c00002","url":null,"abstract":"","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 3","pages":"132–136 132–136"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.5c00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determining the Multivalent Effects of d-Peptide-Based Radiotracers","authors":"Siqi Zhang, Xiaona Sun, Wenhao Liu, Jiang Wu, Yuxuan Wu, Shuo Jiang, Xingkai Wang, Xin Gao, Quan Zuo, Hailong Zhang, Yingzi Zhang, Feng Wang, Rui Wang* and Kuan Hu*, ","doi":"10.1021/cbmi.4c0007110.1021/cbmi.4c00071","DOIUrl":"https://doi.org/10.1021/cbmi.4c00071https://doi.org/10.1021/cbmi.4c00071","url":null,"abstract":"<p >Dextrorotary (<span>d</span>) peptides, composed of <span>d</span>-amino acids, are hyper-resistant to proteolytic hydrolysis, making them valuable ligands with excellent <i>in vivo</i> stability for radiopharmaceutical development. Multimerization is a well-established strategy for enhancing the <i>in vivo</i> performance of <span>l</span>-peptide-based radiopharmaceuticals. However, the effect of multimerization on the <i>in vivo</i> fate of <span>d</span>-peptide-based radiopharmaceuticals remains largely unexplored. Here, we synthesized the <span>d</span>-peptide DPA, which targets PD-L1, along with its dimer (DP2) and trimer (DP3). PET/CT imaging and <i>ex vivo</i> biodistribution studies were performed to delineate the pharmacokinetics and target interactions of [<sup>68</sup>Ga]DPA, [<sup>68</sup>Ga]DP2, and [<sup>68</sup>Ga]DP3 in both normal and tumor-bearing mice. Our results revealed that tumor uptake and kidney retention increased with higher valency ([<sup>68</sup>Ga]DP3 > [<sup>68</sup>Ga]DP2 > [<sup>68</sup>Ga]DPA). No significant differences were observed in the liver, heart, lung, spleen, intestine, or bone among the three radiotracers. Interestingly, a significant reduction of radioactivity in the bloodstream was detected for the [<sup>68</sup>Ga]DP3-treated group compared to the other two groups. Data analysis revealed that chiral configuration of amino acids and the linking chemistry used in multimerization are the two dominant factors in the <i>in vivo</i> fate of <span>d</span>-peptide multimers. These findings indicate that <span>d</span>-peptide multimerization exerts a distinct influence on <i>in vivo</i> profiles compared to <span>l</span>-peptide multimerization. This study deepens our understanding of how mirror-imaged peptides/proteins interact with the living systems, paving the way for the development of radiopharmaceuticals that harness <span>d</span>-peptides as targeting moieties.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 3","pages":"180–190 180–190"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Going Above and Beyond: Achieving High Contrast and Higher Offset through Carbon Dot-Based diaCEST MRI Contrast Agent.","authors":"Shalini Pandey, Arindam Ghosh","doi":"10.1021/cbmi.4c00086","DOIUrl":"10.1021/cbmi.4c00086","url":null,"abstract":"<p><p>Diamagnetic CEST (diaCEST) MRI contrast agents (CAs) have recently gained immense popularity by virtue of the fact that contrast can be switched on or off by merely changing a few experimental parameters, even after the agent is administered. However, the low efficiency and small solute-solvent offset of the contrast-generating exchangeable protons have so far prevented them from becoming a practical option for in vivo applications. Low efficiency demands high dosage, while small offset invites unwanted interference from the endogenous metabolites present in the human body. So far, the strategy for finding efficient diaCEST CAs involved searching for suitable molecules in which the exchangeable protons resonate as far as possible from water and have an optimum exchange rate. Very little effort has been devoted toward designing or converting to an efficient one from a less efficient existing CA. It was recently shown that hydrothermally synthesized carbon nanodots (CDs) have the ability to enhance contrast efficiency and to tune the pH response of certain diaCEST CAs. Here we show that a suitable combination of the synthesis technique and synthesis parameters can simultaneously enhance solute-solvent offset and contrast efficiency. In particular, we demonstrate 300% enhancement in offset and 100% enhancement in efficiency following the formation of carbon-dots from a urea-citric acid mixture.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"123-131"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Going Above and Beyond: Achieving High Contrast and Higher Offset through Carbon Dot-Based diaCEST MRI Contrast Agent","authors":"Shalini Pandey, and , Arindam Ghosh*, ","doi":"10.1021/cbmi.4c0008610.1021/cbmi.4c00086","DOIUrl":"https://doi.org/10.1021/cbmi.4c00086https://doi.org/10.1021/cbmi.4c00086","url":null,"abstract":"<p >Diamagnetic CEST (diaCEST) MRI contrast agents (CAs) have recently gained immense popularity by virtue of the fact that contrast can be switched on or off by merely changing a few experimental parameters, even after the agent is administered. However, the low efficiency and small solute–solvent offset of the contrast-generating exchangeable protons have so far prevented them from becoming a practical option for in vivo applications. Low efficiency demands high dosage, while small offset invites unwanted interference from the endogenous metabolites present in the human body. So far, the strategy for finding efficient diaCEST CAs involved searching for suitable molecules in which the exchangeable protons resonate as far as possible from water and have an optimum exchange rate. Very little effort has been devoted toward designing or converting to an efficient one from a less efficient existing CA. It was recently shown that hydrothermally synthesized carbon nanodots (CDs) have the ability to enhance contrast efficiency and to tune the pH response of certain diaCEST CAs. Here we show that a suitable combination of the synthesis technique and synthesis parameters can simultaneously enhance solute–solvent offset and contrast efficiency. In particular, we demonstrate 300% enhancement in offset and 100% enhancement in efficiency following the formation of carbon-dots from a urea–citric acid mixture.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"123–131 123–131"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of Nanomaterials in Early Imaging and Advanced Treatment of Atherosclerosis.","authors":"Qianru Zhou, Yujie Wang, Guangxiang Si, Xingbiao Chen, Dan Mu, Bing Zhang","doi":"10.1021/cbmi.4c00064","DOIUrl":"10.1021/cbmi.4c00064","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a serious disease that poses a significant threat to the global population. In this review, we analyze the development of AS from multiple perspectives, aiming to elucidate its molecular mechanisms. We also focus on imaging techniques and therapeutic approaches, highlighting the crucial role of nanomaterials in both imaging and therapy for AS. By leveraging their compatibility and targeting capabilities, nanomaterials can be integrated with traditional medical imaging and therapeutic agents to achieve targeted drug delivery, controlled release, and precise localization and imaging of atherosclerotic plaques.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"51-76"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qianru Zhou, Yujie Wang, Guangxiang Si, Xingbiao Chen, Dan Mu* and Bing Zhang*,
{"title":"Application of Nanomaterials in Early Imaging and Advanced Treatment of Atherosclerosis","authors":"Qianru Zhou, Yujie Wang, Guangxiang Si, Xingbiao Chen, Dan Mu* and Bing Zhang*, ","doi":"10.1021/cbmi.4c0006410.1021/cbmi.4c00064","DOIUrl":"https://doi.org/10.1021/cbmi.4c00064https://doi.org/10.1021/cbmi.4c00064","url":null,"abstract":"<p >Atherosclerosis (AS) is a serious disease that poses a significant threat to the global population. In this review, we analyze the development of AS from multiple perspectives, aiming to elucidate its molecular mechanisms. We also focus on imaging techniques and therapeutic approaches, highlighting the crucial role of nanomaterials in both imaging and therapy for AS. By leveraging their compatibility and targeting capabilities, nanomaterials can be integrated with traditional medical imaging and therapeutic agents to achieve targeted drug delivery, controlled release, and precise localization and imaging of atherosclerotic plaques.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"51–76 51–76"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Audrey Van Heest, Yuzhen Wang, Liang Zhang, Lucy A Phillips, Samuel D Karsen, Christine Nelson, Heather L Knight, Stuart J Perper, Stephen O'Brien, Meghan Clements, Victor Z Sun, Andrew Goodearl, Annette Schwartz Sterman, Soumya Mitra
{"title":"Quantitative Assessment of Pulmonary Fibrosis in a Murine Model via a Multimodal Imaging Workflow.","authors":"Audrey Van Heest, Yuzhen Wang, Liang Zhang, Lucy A Phillips, Samuel D Karsen, Christine Nelson, Heather L Knight, Stuart J Perper, Stephen O'Brien, Meghan Clements, Victor Z Sun, Andrew Goodearl, Annette Schwartz Sterman, Soumya Mitra","doi":"10.1021/cbmi.4c00065","DOIUrl":"10.1021/cbmi.4c00065","url":null,"abstract":"<p><p>Disease-recapitulating animal models are valuable tools in preclinical development for the study of compounds. In the case of fibrotic pulmonary diseases such as idiopathic pulmonary fibrosis (IPF), the bleomycin model of lung injury in the mouse is widely used. To evaluate bleomycin-induced changes in the lung, we employed a quantitative, multimodal approach. Using in vivo microcomputed tomography (μCT), we demonstrated radiographic changes associated with disease progression in aeration levels of the lung parenchyma. There exists an unmet need for a quantitative, high-resolution imaging probe to detect pulmonary fibrosis, particularly that can differentiate between inflammatory and fibrotic components of the disease. Matrix remodeling and overexpression of extracellular matrix (ECM) proteins such as collagen and fibronectin are hallmarks of organ fibrosis. A splice variant of fibronectin containing extra domain A (FnEDA) is of particular interest in fibrosis due to its high level of expression in diseased tissue, which is confirmed here using immunohistochemistry (IHC) in mouse and human lungs. An antibody against FnEDA was evaluated for use as an imaging tool, particularly by using in vivo single-photon emission computed tomography (SPECT) and ex vivo near-infrared (NIR) fluorescence imaging. These data were further corroborated with histological tissue staining and fibrosis quantitation based on a Modified Ashcroft (MA) score and a digital image analysis of whole slide lung tissue sections. The fusion of these different approaches represents a robust integrated workflow combining anatomical and molecular imaging technologies to enable the visualization and quantitation of disease activity and treatment response with an inhibitor of the TGFβ signaling pathway.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"85-94"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}