Abstract: Lipid nanoparticles for delivering mRNA therapeutics hold immense promise for the treatment of a wide range of lung-associated diseases. However, the lack of effective methodologies capable of identifying the pulmonary delivery profile of chemically distinct lipid libraries poses a significant obstacle to the advancement of mRNA therapeutics. Here we report the implementation of a barcoded high-throughput screening system as a means to identify the lung-targeting efficacy of cationic, degradable lipid-like materials. We combinatorially synthesize 180 cationic, degradable lipids which are initially screened in vitro. We then use barcoding technology to quantify how the selected 96 distinct lipid nanoparticles deliver DNA barcodes in vivo. The top-performing nanoparticle formulation delivering Cas9-based genetic editors exhibits therapeutic potential for antiangiogenic cancer therapy within a lung tumor model in female mice. These data demonstrate that employing high-throughput barcoding technology as a screening tool for identifying nanoparticles with lung tropism holds potential for the development of next-generation extrahepatic delivery platforms.
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With trichlorophosphate; In ethyl acetate; at 20.0℃; for 1.0h;Cooling with ice;
In a 1 L single-necked flask, <strong>[6099-90-7]phloroglucinol dihydrate</strong> (38.6 g, 0.238 mol), DMF (55.03 mL, 0.714 mol), ethyl acetate (450 mL),Phosphorus oxychloride (66.32 mL, 0.714 mol) was slowly added dropwise under ice bath.After the addition, transfer to room temperature for 1 h, filter, wash with ethyl acetate, place the filter cake in a 500 mL single-necked flask, add water (150 mL), protect with nitrogen, warm to reflux and maintain for 10 min, then cool to room temperature and then refrigerate in the refrigerator. 1h,Filter, wash with water, collect the filter cake and dry in vacuo without further purification.A white solid was obtained in 36 g, yield 98%.
2-(2,4,6-trihydroxyphenyl)-1H-benzo[d]imidazole-5-sulfonic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With sodium metabisulfite; In ethanol; water; for 24h;Reflux;
General procedure: To a solution of the appropriate 3,4-diaminobenzene derivative (1ad)(2 mmol) in ethanol (15 mL) 2.85 N aqueous solution of sodium metabisulphite (1.6 mL) and the appropriate substituted arylaldehyde(2 mmol) were added. The reaction mixture was heated at reflux for 24 h. The solvent was then evaporated under reduced pressure. The residue was added with HCl 1 N (10 mL), the formed precipitate was filtered off, washed with water (3×10 mL) and purified by crystallization from the adequate solvent to give the title compounds.Following the general procedure benzimidazoles 3 [19], 4 [20], 5 [21],7 [24], 6, 32 and 33 [15] were prepared and their analytical and spectral data are in agreement with those reported in literature.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
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