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Encapsulation of Apoptotic Proteins in Lipid Nanoparticles to Induce Death of Cancer Cells
Biotechnology and Bioprocess Engineering ( IF 2.5 ) Pub Date : 2020-03-20 , DOI: 10.1007/s12257-019-0409-7
Chun-Sik Bae , Chang-Min Lee , Taeho Ahn

According to previous reports, cationic nanoparticles (cNPs) consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), a cationic lipid, without any cargos, induce generation of reactive oxygen species (ROS) and toxicity in cells. We investigated the effect of DOTAP-based cNPs containing encapsulated human pro-apoptotic proteins (P-cNPs), tBid, Bax, or cytochrome c (Cyt c) on the death of HepG2, cancer cells. Upon the treatment to cells, cNPs containing Cyt c-cargo were the most effective in inducing cell death, followed by tBid- and Bax-cNPs. Among three P-cNPs, Cyt c-cNPs also induced the highest levels of ROS production and caspase-3 activity in the cells under the treatment with the same DOTAP concentration. The incorporation of dioleoylglycerol (DOG), a neutral phospholipid, in cNPs at the expense of DOTAP resulted in an increased amount of the encapsulated protein and consequently enhanced cell death in a DOG concentration-dependent manner. Thus, the present cNP formulation with protein cargo may elicit apoptotic effects in cancer cells and serve as a rational background for the preparation of cationic lipid-based NP formulation for cancer treatment.



中文翻译:

脂质纳米粒中凋亡蛋白的包裹诱导癌细胞死亡

根据以前的报道,由阳离子脂质组成的1,2-二油酰基-3-三甲基铵-丙烷(DOTAP)组成的阳离子纳米颗粒(cNPs)可以诱导活性氧(ROS)的产生和细胞毒性。我们调查了包含封装的人类促凋亡蛋白(P-cNPs),tBid,Bax或细胞色素c(Cyt c)的基于DOTAP的cNP对HepG2癌细胞死亡的影响。经细胞处理后,含有Cyt c-货物的cNPs在诱导细胞死亡方面最有效,其次是tBid-和Bax-cNPs。在三个P-cNP中,Cyt c在相同的DOTAP浓度下,-cNPs还诱导了细胞中最高水平的ROS产生和caspase-3活性。以DOTAP为代价在cNPs中掺入油酰甘油(DOG)(一种中性磷脂)会导致所包封的蛋白质数量增加,从而以DOG浓度依赖性方式增加细胞死亡。因此,具有蛋白质货物的本发明cNP制剂可以在癌细胞中引起凋亡作用,并且可以作为制备用于癌症治疗的基于阳离子脂质的NP制剂的合理背景。

更新日期:2020-04-18
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