{"title":"Synthesis and Characterization of a Novel Photocleavable Fluorescent Dye Dyad for Diffusion Imaging","authors":"Damian Schöngen, and , Dominik Wöll*, ","doi":"10.1021/cbmi.4c0008410.1021/cbmi.4c00084","DOIUrl":"https://doi.org/10.1021/cbmi.4c00084https://doi.org/10.1021/cbmi.4c00084","url":null,"abstract":"<p >We report the synthesis and characterization of a photocleavable fluorescent dye dyad. The two constituting dyes show a large spectral overlap and are in close proximity to each other, leading to efficient Förster Resonance Energy Transfer (FRET). Photocleavage of the dyad and the subsequent independent diffusion of both fluorophores qualifies the system to be used for high accuracy diffusion measurements. In contrast to previous work, the dyad reported here can be applied in polar solvents and cleaved by UV-A light. Beneficially, the photolabile linker provides two orthogonal labeling sites for various commercially available fluorescent labels. In this work, we chose the cationic organic dyes ATTO565 and ATTO647N. We outline the synthesis and spectral characterization of the system with UV–Vis and fluorescence spectroscopy as well as fluorescence lifetime and fluorescence quantum yield measurements. Furthermore, we performed proof-of-principle microscopy experiments to demonstrate its capability in polyvinyl acetate films.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 3","pages":"199–207 199–207"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675804","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":"Synthesis and Characterization of a Novel Photocleavable Fluorescent Dye Dyad for Diffusion Imaging.","authors":"Damian Schöngen, Dominik Wöll","doi":"10.1021/cbmi.4c00084","DOIUrl":"10.1021/cbmi.4c00084","url":null,"abstract":"<p><p>We report the synthesis and characterization of a photocleavable fluorescent dye dyad. The two constituting dyes show a large spectral overlap and are in close proximity to each other, leading to efficient Förster Resonance Energy Transfer (FRET). Photocleavage of the dyad and the subsequent independent diffusion of both fluorophores qualifies the system to be used for high accuracy diffusion measurements. In contrast to previous work, the dyad reported here can be applied in polar solvents and cleaved by UV-A light. Beneficially, the photolabile linker provides two orthogonal labeling sites for various commercially available fluorescent labels. In this work, we chose the cationic organic dyes ATTO565 and ATTO647N. We outline the synthesis and spectral characterization of the system with UV-Vis and fluorescence spectroscopy as well as fluorescence lifetime and fluorescence quantum yield measurements. Furthermore, we performed proof-of-principle microscopy experiments to demonstrate its capability in polyvinyl acetate films.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 3","pages":"199-207"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733018","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":"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, Dingbin Liu","doi":"10.1021/cbmi.4c00085","DOIUrl":"10.1021/cbmi.4c00085","url":null,"abstract":"<p><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"},"PeriodicalIF":0.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732937","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":"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}
{"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}
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":"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}