DSPE-PEG-anisamide修饰纳米颗粒的配体靶向与空间稳定性应用
文献资料:反义寡脱氧核苷酸和小抑制RNA靶点递送进非小癌细胞肺癌癌细胞微信链接://pubs.acs.org/doi/abs/10.1021/mp060039w我们:李世达,枯黄提要:经过反义寡脱氧核苷酸 (AS-ODN) 或小要素 RNA (siRNA) 保健法开展通过性什么是基因抑制性极可能*过去的肿瘤药物没法治疗的病毒。然后,反义保健法仍然在生理变化液中的可靠性好和体细胞系内摄取量有限制的而会受到阻挡。要处理这类话题,我门實驗室搭建了了种配体靶点和空间可靠的nm颗料药制剂。人们的癌症体细胞系一般说来过描述 σ 蛋白激酶,故而行用特殊配体(举例说明茴香酰胺)开展靶点*。将针对于人類长期生存素的 AS-ODN 或 siRNA 与质粒 DNA(小公牛胸腺 DNA)比调,最后与鱼精蛋白质(一个带高正自由电荷的肽)软型。将得到科粒用由 DOTAP 和热量(摩尔比 1:1)组合成的阳正亚铁离子脂质体包被,以获得了 LPD(脂质体-聚阳正亚铁离子-DNA)纳米技术技术科粒。最后,用后添加图片法将预制板的LPD纳米技术技术a粒子与DSPE-PEG-茴香酰胺(我科学试验室最早的时候开发管理的一个PEG化配体脂质)在一起孵育,构建配体靶向药物性和三维空间稳界定性。同时化学上合成了DSPE-PEG包复的非靶点微米a离子做为差表。在Survivin mRNA变动、Survivin球蛋白变动、几率会导致*神经元凋亡的专业能力、*神经元生长期能够抑制各种治疗后的*神经元对*癌口服药的化学上增敏使用来法测微米a离子的反义特异性。他们感觉,PEG化微米a离子的*神经元递送和反义特异性是字段依耐性的,以及依耐于茴香酰胺配体的会出现。靶点PEG化微米a离子对寡核苷酸的摄取量几率会被否则的矿酸配体争夺。他们的结论证实,配体靶点和室内空间增强的微米a离子就能够目的性地将 AS-ODN 和 siRNA 递邮到癌症神经元中做好*。AbstractAbstract ImageSelective gene inhibition by antisense oligodeoxynucleotide (AS-ODN) or by small interference RNA (siRNA) therapeutics promises the treatment of diseases that cannot be cured by conventional drugs. However, antisense therapy is hindered due to poor stability in physiological fluids and limited intracellular uptake. To address these problems, a ligand targeted and sterically stabilized nanoparticle formulation has been developed in our lab. Human lung cancer cells often overexpress the sigma receptor and, thus, can be targeted with a specific ligand such as anisamide. AS-ODN or siRNA against human survivin was mixed with a carrier DNA, calf thymus DNA, before complexing with protamine, a highly positively charged peptide. The resulting particles were coated with cationic liposomes consisting of DOTAP and cholesterol (1:1, molar ratio) to obtain LPD (liposome−polycation−DNA) nanoparticles. Ligand targeting and steric stabilization were then introduced by incubating preformed LPD nanoparticles with DSPE-PEG-anisamide, a PEGylated ligand lipid developed earlier in our lab, by the postinsertion method. Nontargeted nanoparticles coated with DSPE-PEG were also prepared as a control. Antisense activities of nanoparticles were determined by survivin mRNA down-regulation, survivin protein down-regulation, ability to trigger apoptosis in tumor cells, tumor cell growth inhibition, and chemosensitization of the treated tumor cells to anticancer drugs. We found that tumor cell delivery and antisense activity of PEGylated nanoparticles were sequence dependent and rely on the presence of anisamide ligand. The uptake of oligonucleotide in targeted, PEGylated nanoparticles could be competed by excess free ligand. Our results suggest that the ligand targeted and sterically stabilized nanoparticles can provide a selective delivery of AS-ODN and siRNA into lung cancer cells for therapy.