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Visualizing Kinetically Robust Co <sup>III</sup><sub/>4</sub> L <sub/>6</sub> Assemblies <i>In Vivo</i> : SPECT Imaging of the Encapsulated [ <sup>99m</sup> Tc]TcO <sub/>4</sub><sup>?</sup> Anion
摘要： Non-covalent encapsulation is an attractive approach for modifying the efficacy and physiochemical properties of both therapeutic and diagnostic species. Abiotic self-assembled constructs have shown promise, yet many hurdles between in vitro and (pre)clinical studies remain, not least the challenges associated with maintaining the macromolecular, hollow structure under non-equilibrium conditions. Using a kinetically robust CoIII4L6 tetrahedron we now show the feasibility of encapsulating the most widely used precursor in clinical nuclear diagnostic imaging, the gamma emitting [99mTc]TcO4? anion, under conditions compatible with in vivo administration. Subsequent SPECT imaging of the caged-anion reveals a marked change in the biodistribution compared to the thyroid-accumulating free oxo-anion, thus moving clinical applications of (metallo)supramolecular species a step closer.
关键词： SPECT imaging,biodistribution,clinical applications,CoIII4L6 tetrahedron,Non-covalent encapsulation
更新于2025-09-09 09:28:46
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Effect of Polyethylene Glycol Surface Charge Functionalization of SWCNT on the in vitro and in vivo Nanotoxicity and Biodistribution Monitored Noninvasively using MRI
摘要： The current study evaluated in vitro and in vivo toxicity of carboxyl or amine PEG surface functionalization of single walled carbon nanotubes (SWCNTs). Assessments of cytotoxicity, genotoxicity, immunotoxicity and oxidative stress were performed in vitro and in vivo (in a one-month follow-up study). The SWCNT biodistribution was investigated using noninvasive MRI. Results confirmed the enhanced biocompatibility of PEG-functionalized SWCNTs compared to non-functionalized materials with significant decreases (p<0.05) in the percentage of cell viability and increases in ROS generation, mitochondrial membrane potential, cell apoptosis, oxidative stress generation and oxidative DNA damage in vitro. PEG-functionalized SWCNTs with amine terminals were found to induce prominent increases in ROS generation, mitochondrial membrane potential, and oxidative stress compared to carboxy functionalized SWCNTs. No significant difference in the biodistribution of either PEG-COOH or PEG-NH2 functionalized SWCNTs was observed in MRI. In vivo assessments revealed a statistically significant increase (p<0.05) in oxidative stress as early as 24 h in serum and liver; however, all values normalized at 2 weeks’ investigation time point. DNA damage was minimal with either PEG-COOH or PEG-NH2 functionalized SWCNTs after two weeks’ exposure. The negatively charged SWCNTs caused lesser DNA damage compared to positively charged samples. Carboxy-functionalized SWCNTs did not caused substantial changes in inflammatory mediators and were found to be significantly safer than non-functionalized SWCNTs and may pave the way for novel biomedical applications in cancer diagnosis and therapy.
关键词： Nanotoxicity,Cytotoxicity,Carbon nanotubes,In vivo biodistribution,Magnetic Resonance Imaging
更新于2025-09-04 15:30:14