DSPE-PEG-anisamide修饰纳米颗粒的配体靶向与空间稳定性应用
期刊论文:反义寡脱氧核苷酸和小侵扰RNA靶向治疗递送进非小受损细胞肺癌受损细胞外部链接://pubs.acs.org/doi/abs/10.1021/mp060039w我们:李世达,叶黄英文论文:使用反义寡脱氧核苷酸 (AS-ODN) 或小干预 RNA (siRNA) 方式实行选泽性dna克制一般*民俗用药时未冶愈的常见疾病。所以,反义方式会因为在生理方面液中的固定性性好和组织内摄食比较有限而受影响。要为彻底解决这么多方面,我门实践室规划设计了种配体靶向药物药物和区域空间固定性的纳米技术颗料药制剂。人肺癌患者组织一般是过表现 σ 多巴胺受体,故而不错用单一配体(比如说茴香酰胺)实行靶向药物药物*。将涉及人存在素的 AS-ODN 或 siRNA 与形式 DNA(小公牛胸腺 DNA)比调,第三与鱼精血清(种带高正电荷量的肽)分手后复合。将增值税顆粒用由 DOTAP 和热量(摩尔比 1:1)组合而成的阳亚铁铁离子脂质体包被,以赚取 LPD(脂质体-聚阳亚铁铁离子-DNA)nm顆粒。第三,用后进到这一领域法将预制混凝土的LPDnm塑料再生颗粒与DSPE-PEG-茴香酰胺(咱们研究室早期时候设计规划的种PEG化配体脂质)一起去孵育,添加配体靶向疗法性和环境空间保持稳相关性。直接光催化原理了DSPE-PEG包塑的非靶向治疗疗法性药物nm阿尔法离子作比。利用Survivin mRNA调低、Survivin球蛋白调低、激发*癌上皮组织体细胞核凋亡的性能、*癌上皮组织体细胞核衍生抑制性以其外理后的*癌上皮组织体细胞核对*癌性药物的生物学增敏影响来测定方法nm阿尔法离子的反义活力性。我国找到,PEG化nm阿尔法离子的*癌上皮组织体细胞核递送和反义活力性是字段依靠性的,然后依靠于茴香酰胺配体的有。靶向治疗疗法性药物PEG化nm阿尔法离子对寡核苷酸的摄取量需要会被吃太多的徘徊配体行业竞争。我国的效果表面,配体靶向治疗疗法性药物和环境空间安稳的nm阿尔法离子需要抉择性地将 AS-ODN 和 siRNA 递送至癌症癌上皮组织体细胞核中通过*。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.



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