The present study focuses on the development of a sensitive and specific approach for the visualization of sentinel lymph nodes draining the tumor using ultrabright 200‐nm fluorescent nanodiamonds (FNDs) equipped with a designed targeting surface architecture. The FNDs with a narrow size distribution are isolated by differential centrifugation, colloidally stabilized with alkyne‐functionalized poly(glycerol) and modified with a polyvalent array of mannose (FND‐p‐Man). In vitro experiments demonstrate an outstanding increase of the particle internalization by the mannose receptor CD206 (MR) and no significant toxicity. MR involvement is confirmed by blocking ligand binding with mannan and a 15.2 mAb (specific anti‐MR) in J774A.1 mouse macrophage cell line. In vivo mouse experiments confirm increased retention of FND‐p‐Man in sentinel lymph nodes of both healthy and B16 melanoma bearing animals. These results suggest that FND‐p‐Man has potential as a tracer for lymph node visualization in locoregional perioperative cancer diagnostics and as a tool for endoscopic/robotic fluorescence‐guided surgery.
Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians, affecting more than 100,000 individuals worldwide. It is caused by pathogenic variants in the gene encoding CFTR, an anion channel at the plasma membrane of epithelial and other cells. Many CF pathogenic variants disrupt the biosynthesis and trafficking of CFTR or reduce its ion channel function. The most frequent mutation, loss of a phenylalanine at position 508 (F508del), leads to misfolding, retention in the endoplasmic reticulum, and premature degradation of the protein. The therapeutics available for treating CF lung disease include antibiotics, mucolytics, bronchodilators, physiotherapy, and most recently CFTR modulators. To date, no cure for this life shortening disease has been found. Treatment with the Triple combination drug therapy, TRIKAFTA®, is composed of three drugs: Elexacaftor (VX-445), Tezacaftor (VX-661) and Ivacaftor (VX-770). This therapy, benefits persons with CF, improving their weight, lung function, energy levels (as defined by reduced fatigue), and overall quality of life. We examined the effect of combining LAU-7b oral treatment and Triple therapy combination on lung function in a F508deltm1EUR mouse model that displays lung abnormalities relevant to human CF. We assessed lung function, lung histopathology, protein oxidation, lipid oxidation, and fatty acid and lipid profiles in F508deltm1EUR mice.
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