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Combinatorial Library of Cyclic Benzylidene Acetal-Containing pH-Responsive Lipidoid Nanoparticles for Intracellular mRNA Delivery.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-06-10 , DOI: 10.1021/acs.bioconjchem.0c00295 Yamin Li 1 , Raissa Li 1 , Anirban Chakraborty 1 , Roza Ogurlu 1 , Xuewei Zhao 1 , Jinjin Chen 1 , Qiaobing Xu 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-06-10 , DOI: 10.1021/acs.bioconjchem.0c00295 Yamin Li 1 , Raissa Li 1 , Anirban Chakraborty 1 , Roza Ogurlu 1 , Xuewei Zhao 1 , Jinjin Chen 1 , Qiaobing Xu 1
Affiliation
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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 photoresponsive 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 multistep 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 R-O16CBA lipidoid nanoparticles were then fabricated with different formulations of DOPE and cholesterol and tested in vitro for intracellular mRNA delivery.
中文翻译：
用于细胞内 mRNA 递送的含有环状亚苄基乙缩醛的 pH 响应类脂质纳米颗粒的组合文库。
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。刺激响应类脂质纳米颗粒能够进一步提高递送效率并降低载体诱导的毒性。我们小组之前开发了用于小分子和生物制剂递送的类脂质纳米颗粒的还原和光响应组合库。在这里，我们描述了一个新的 pH 响应类脂质纳米粒子库的合成、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环状亚苄基乙缩醛阳离子类脂质 (R-O16CBA)，并通过 NMR 和 MS 对其进行了表征。使用 NMR、MS、DLS 和 TEM 研究了酸引发的类脂质降解。体外用于细胞内 mRNA 递送。
更新日期：2020-07-15
中文翻译：
用于细胞内 mRNA 递送的含有环状亚苄基乙缩醛的 pH 响应类脂质纳米颗粒的组合文库。
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。刺激响应类脂质纳米颗粒能够进一步提高递送效率并降低载体诱导的毒性。我们小组之前开发了用于小分子和生物制剂递送的类脂质纳米颗粒的还原和光响应组合库。在这里，我们描述了一个新的 pH 响应类脂质纳米粒子库的合成、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环状亚苄基乙缩醛阳离子类脂质 (R-O16CBA)，并通过 NMR 和 MS 对其进行了表征。使用 NMR、MS、DLS 和 TEM 研究了酸引发的类脂质降解。体外用于细胞内 mRNA 递送。
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