Combinatorial Library of Cyclic Benzylidene Acetal-Containing pH-Responsive Lipidoid Nanoparticles for Intracellular mRNA Delivery.
Combinatorial Library of Cyclic Benzylidene Acetal-Containing pH-Responsive Lipidoid Nanoparticles for Intracellular mRNA Delivery.
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DOI：
10.1021/acs.bioconjchem.0c00295
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发表时间：
2020-07-15
影响因子：
4.7
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Li Y;Li R;Chakraborty A;Ogurlu R;Zhao X;Chen J;Xu Q
类脂质纳米颗粒已被证明可有效用于小分子药物、蛋白质和核酸的细胞内递送。刺激响应性类艾杜糖纳米颗粒能够进一步提高递送功效并降低载体诱导的毒性。我们的小组先前开发了用于小分子和生物制剂递送的类胡萝卜素纳米颗粒的还原和光响应组合文库。在此，我们描述了一个新的pH响应性类胡萝卜素纳米颗粒库的合成，表征和细胞内mRNA递送应用。通过多步反应合成了可酸降解的含环亚苄基缩醛的阳离子类胡萝卜素（R-O 16 CBA），并利用NMR、MS、DLS和TEM研究了该类胡萝卜素的酸引发降解。结果表明，R-O 16 CBA类胡萝卜素在pH 5时可完全降解。然后用不同的DOPE和胆固醇制剂制备O 16 CBA类胡萝卜素纳米颗粒，并在体外测试细胞内mRNA递送。
Lipidoid nanoparticles have been demonstrated to be effective for intracellular delivery of small molecule drugs, proteins, and nucleic acids. Stimuli-responsive lipidoid nanoparticles are able to further improve delivery efficacy and reduce carrier-induced toxicity. Our group previously developed reduction- and photo-responsive combinatorial libraries of lipidoid nanoparticles for small molecule and biologics delivery. Herein, we describe the synthesis, characterization, and intracellular mRNA delivery application of a new library of pH-responsive lipidoid nanoparticles. The acid-degradable cyclic benzylidene acetal-containing cationic lipidoids (R-O16CBA) were synthesized through a multi-step reaction and characterized by NMR and MS. The acid-triggered degradation of lipidoids was studied using NMR, MS, DLS and TEM. The results revealed that the R-O16CBA lipidoid can be completely degraded at pH 5. The O16CBA lipidoid nanoparticles were then fabricated with different formulations of DOPE and cholesterol and tested in vitro for intracellular mRNA delivery.
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