Chemical & Biomedical Imaging最新文献

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.

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.

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 in vivo 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.

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 in vivo 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.

Dextrorotary (d) peptides, composed of d-amino acids, are hyper-resistant to proteolytic hydrolysis, making them valuable ligands with excellent in vivo stability for radiopharmaceutical development. Multimerization is a well-established strategy for enhancing the in vivo performance of l-peptide-based radiopharmaceuticals. However, the effect of multimerization on the in vivo 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 ex vivo biodistribution studies were performed to delineate the pharmacokinetics and target interactions of [⁶⁸Ga]DPA, [⁶⁸Ga]DP2, and [⁶⁸Ga]DP3 in both normal and tumor-bearing mice. Our results revealed that tumor uptake and kidney retention increased with higher valency ([⁶⁸Ga]DP3 > [⁶⁸Ga]DP2 > [⁶⁸Ga]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 [⁶⁸Ga]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 in vivo fate of d-peptide multimers. These findings indicate that d-peptide multimerization exerts a distinct influence on in vivo 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.

Dextrorotary (d) peptides, composed of d-amino acids, are hyper-resistant to proteolytic hydrolysis, making them valuable ligands with excellent in vivo stability for radiopharmaceutical development. Multimerization is a well-established strategy for enhancing the in vivo performance of l-peptide-based radiopharmaceuticals. However, the effect of multimerization on the in vivo 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 ex vivo biodistribution studies were performed to delineate the pharmacokinetics and target interactions of [⁶⁸Ga]DPA, [⁶⁸Ga]DP2, and [⁶⁸Ga]DP3 in both normal and tumor-bearing mice. Our results revealed that tumor uptake and kidney retention increased with higher valency ([⁶⁸Ga]DP3 > [⁶⁸Ga]DP2 > [⁶⁸Ga]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 [⁶⁸Ga]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 in vivo fate of d-peptide multimers. These findings indicate that d-peptide multimerization exerts a distinct influence on in vivo 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.

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.

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.