The Education Ministry Key Laboratory of Resource Chemistry, Department of Chemistry, Life and Environmental Science College, Shanghai Normal University, Shanghai 200234, China.
ACS Appl Mater Interfaces. 2013 Feb;5(3):1131-6. doi: 10.1021/am3028926. Epub 2013 Jan 28.
Antisense oligodeoxynucleotides (ASODNs) can bind to some specific RNA of survivin can prevent the mRNA translation at the genetic level, which will inhibit survivin expression and make the cancer cells apoptosis. However, the ASODNs-based therapies are hampered by their instability to cellular nuclease and their weak intracellular penetration. Here we reported a calcium phosphate (CP)-based carrier to achieve efficient delivery of ASODNs into cells. In this study, we used a facile microemulsion approach to prepare spherical and porous ASODNs-CP nanoparticles (ASODNS-CPNPs) with the size of 50-70 nm in diameter, and their structure, morphology and composition were characterized by TEM, XRD, FTIR, ICP and DLS, UV-Vis spectroscopy and agarose gel electrophoresis. The results indicated that the nanoparticles have a high ASODNs loading capacity. Furthermore, cellular uptake and delivery efficiency of the ASODNS-CPNPs, as well as cellular apoptosis induced by the ASODNs doping into the calcium phosphate nanoparticles, were investigated by confocal laser scanning microscopy, biological TEM, flow cytometry, and MTT assay. Efficient intracellular delivery of the nanoparticles was observed. All these results suggested that the prepared calcium phosphate nanoparticles could be used as a promising biocarrier for delivery of ASODNs.
反义寡核苷酸（ASODNs）可以与生存素的某些特定 RNA 结合，在基因水平上阻止 mRNA 的翻译，从而抑制生存素的表达并使癌细胞凋亡。然而，基于 ASODNs 的治疗受到其对细胞核酸酶的不稳定性和弱细胞内穿透性的阻碍。在这里，我们报道了一种基于磷酸钙（CP）的载体，以实现 ASODNs 向细胞的有效递药。在这项研究中，我们使用简便的微乳液方法制备了直径为 50-70nm 的球形多孔 ASODNs-CP 纳米颗粒（ASODNS-CPNPs），并通过 TEM、XRD、FTIR、ICP 和 DLS、UV-Vis 光谱和琼脂糖凝胶电泳对其结构、形态和组成进行了表征。结果表明，纳米颗粒具有高的 ASODNs 负载能力。此外，通过共聚焦激光扫描显微镜、生物 TEM、流式细胞术和 MTT 测定研究了 ASODNS-CPNPs 的细胞摄取和递药效率以及掺杂到磷酸钙纳米颗粒中的 ASODNs 诱导的细胞凋亡。观察到了纳米颗粒的有效细胞内递药。所有这些结果表明，所制备的磷酸钙纳米颗粒可用作 ASODNs 递药的有前途的生物载体。
