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Self-Assembling Lipid–Peptide Hybrid Nanoparticles of Phospholipid–Nonaarginine Conjugates for Enhanced Delivery of Nucleic Acid Therapeutics
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-10-09 00:00:00 , DOI: 10.1021/acs.biomac.7b01084 Ji Hee Kang 1 , Gantumur Battogtokh 1 , Young Tag Ko 1
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-10-09 00:00:00 , DOI: 10.1021/acs.biomac.7b01084 Ji Hee Kang 1 , Gantumur Battogtokh 1 , Young Tag Ko 1
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Despite potential applications of nucleic acid therapeutics, the lack of effective delivery systems hinders their clinical application. To overcome the barriers to nucleic acid delivery, we previously reported nanoparticles using phospholipid–polyethylenimine conjugates. However, toxicity of polyethylenimine remains as a problematic issue. Herein, we proposed to substitute the polyethylenimine with arginine-rich peptide to obtain a less-toxic carrier system. Nonaarginine was conjugated to the distal end of phospholipid hydrocarbon chains leading to phospholipid–nonaarginine conjugates (PL9R) and then lipid–peptide hybrid nanoparticles carrying oligonucleotide therapeutics (hNP) were constructed by self-assembly process. The hNP were further modified with cell penetrating Tat peptide (T-hNP) to enhance cellular uptake. The PL9R was less cytotoxic, and the hNP showed high loading capacity and colloidal stability. The T-hNP showed higher cellular uptake and transfection efficiency and effective accumulation to tumor tissue and silencing effect in tumor bearing mice. Altogether, T-hNP could provide a promising nanocarrier for nucleic acid therapeutics.
中文翻译：
自组装的磷脂-去甲精氨酸的脂质-肽杂合纳米颗粒可增强核酸治疗剂的递送。
尽管核酸治疗剂有潜在的应用，但是缺乏有效的递送系统阻碍了其临床应用。为了克服核酸传递的障碍，我们先前报道了使用磷脂-聚乙烯亚胺共轭物的纳米颗粒。但是，聚乙烯亚胺的毒性仍然是一个有问题的问题。在本文中，我们提出用富含精氨酸的肽代替聚乙烯亚胺以获得毒性较小的载体系统。将壬精氨酸偶联至磷脂烃链的末端，形成磷脂-壬精氨酸偶联物（PL9R），然后通过自组装过程构建携带寡核苷酸治疗剂（hNP）的脂质-肽杂合纳米颗粒。用穿透细胞的Tat肽（T-hNP）进一步修饰hNP，以增强细胞摄取。PL9R的细胞毒性较小，hNP具有较高的负载能力和胶体稳定性。T-hNP在荷瘤小鼠中表现出更高的细胞摄取和转染效率以及对肿瘤组织的有效积累和沉默作用。总而言之，T-hNP可以为核酸治疗提供有希望的纳米载体。
更新日期：2017-10-09
中文翻译：
自组装的磷脂-去甲精氨酸的脂质-肽杂合纳米颗粒可增强核酸治疗剂的递送。
尽管核酸治疗剂有潜在的应用，但是缺乏有效的递送系统阻碍了其临床应用。为了克服核酸传递的障碍，我们先前报道了使用磷脂-聚乙烯亚胺共轭物的纳米颗粒。但是，聚乙烯亚胺的毒性仍然是一个有问题的问题。在本文中，我们提出用富含精氨酸的肽代替聚乙烯亚胺以获得毒性较小的载体系统。将壬精氨酸偶联至磷脂烃链的末端，形成磷脂-壬精氨酸偶联物（PL9R），然后通过自组装过程构建携带寡核苷酸治疗剂（hNP）的脂质-肽杂合纳米颗粒。用穿透细胞的Tat肽（T-hNP）进一步修饰hNP，以增强细胞摄取。PL9R的细胞毒性较小，hNP具有较高的负载能力和胶体稳定性。T-hNP在荷瘤小鼠中表现出更高的细胞摄取和转染效率以及对肿瘤组织的有效积累和沉默作用。总而言之，T-hNP可以为核酸治疗提供有希望的纳米载体。
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