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Capture and Detection of Fentanyl with Thiolated Cucurbit[7]uril Macrocycles on Silver NanoparticlesFree, publicly-accessible full text available May 10, 2025
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Free, publicly-accessible full text available March 20, 2025
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Abstract The management of diabetes in a manner offering autonomous insulin therapy responsive to glucose‐directed need, and moreover with a dosing schedule amenable to facile administration, remains an ongoing goal to improve the standard of care. While basal insulins with reduced dosing frequency, even once‐weekly administration, are on the horizon, there is still no approved therapy that offers glucose‐responsive insulin function. Herein, a nanoscale complex combining both electrostatic‐ and dynamic‐covalent interactions between a synthetic dendrimer carrier and an insulin analogue modified with a high‐affinity glucose‐binding motif yields an injectable insulin depot affording both glucose‐directed and long‐lasting insulin availability. Following a single injection, it is even possible to control blood glucose for at least one week in diabetic swine subjected to daily oral glucose challenges. Measurements of serum insulin concentration in response to challenge show increases in insulin corresponding to elevated blood glucose levels, an uncommon finding even in preclinical work on glucose‐responsive insulin. Accordingly, the subcutaneous nanocomplex that results from combining electrostatic‐ and dynamic‐covalent interactions between a modified insulin and a synthetic dendrimer carrier affords a glucose‐responsive insulin depot for week‐long control following a single routine injection.
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Soft materials that change form or function in response to environmental or user-applied stimuli have a wide range of biomedical applications ( 1 ). Gels can form in water from weakly interacting molecules but can return to the state of a flowing liquid suspension, known as a sol, upon changes in the concentration of the molecules or the applied temperature. This behavior is known as a reentrant phase transition. A gel-to-sol phase transition typically arises from a reduction in concentration, meaning that a gel becomes a sol upon dilution and a sol becomes a gel with increased concentration. On page 213 of this issue, Su et al. ( 2 ) demonstrate a system that exhibits a sol-to-gel transition when diluted, inverting the common behavior of gels. Their observations offer insight into systems that undergo reentrant phase transitions in biology.more » « less