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ACS Nano:核酸药物新型纳米载体问世

来源:中国科学报 2012-02-03 14:00

近日,美国化学学会期刊《ACS纳米》发布的一项研究成果表明,中科院上海应用物理研究所物理生物学实验室的樊春海与黄庆课题组合作发展了两种新型的纳米载运体系。他们将具有免疫刺激效用的CpG寡核苷酸药物偶联到纳米结构上,发现其可有效地被哺乳动物免疫细胞摄取,并刺激后者产生免疫反应而释放细胞因子。

据介绍,CpG寡核苷酸可通过TLR9信号通路有效引发哺乳动物免疫反应,因此可作为一种良好的免疫佐剂用于抗感染和肿瘤等的辅助。然而,人工合成的CpG寡核苷酸通常难以进入细胞,如何寻找稳定、高活性和生物相容性好的载运体系是CpG药物应用的关键。

纳米金粒子是一种生物相容的纳米材料,其表面可负载大量的巯基修饰的寡核苷酸。研究表明,当CpG寡核苷酸负载到纳米金粒子表面后,能够很容易地被细胞内吞,并产生显著的免疫刺激作用。其刺激产生的多种细胞因子的浓度较裸寡核苷酸提高了两个数量级,且显著高于商品化的载运试剂脂质体。

研究发现,由于稳定性与摄取效率的同步提高,这种纳米载体极大增强了CpG寡核苷酸的免疫刺激效果。同时,DNA纳米结构本身就是核酸分子,容易与待载运核酸分子偶联,且在体内具有可降解、无免疫原性等优点,因而在疾病诊疗中具有广泛的应用前景。(生物谷 Bioon.com)

Self-Assembled Multivalent DNA Nanostructures for Noninvasive Intracellular Delivery of Immunostimulatory CpG Oligonucleotides

Jiang Li,Hao Pei,Bing Zhu,Le Liang,Min Wei,Yao He,Nan Chen,Di Li,Qing Huang,Chunhai Fan,

Designed oligonucleotides can self-assemble into DNA nanostructures with well-defined structures and uniform sizes, which provide unprecedented opportunities for biosensing, molecular imaging, and drug delivery. In this work, we have developed functional, multivalent DNA nanostructures by appending unmethylated CpG motifs to three-dimensional DNA tetrahedra. These small-sized functional nanostructures are compact, mechanically stable, and noncytotoxic. We have demonstrated that DNA nanostructures are resistant to nuclease degradation and remain substantially intact in fetal bovine serum and in cells for at least several hours. Significantly, these functional nanostructures can noninvasively and efficiently enter macrophage-like RAW264.7 cells without the aid of transfection agents. After they are uptaken by cells, CpG motifs are recognized by the Toll-like receptor 9 (TLR9) that activates downstream pathways to induce immunostimulatory effects, producing high-level secretion of various pro-inflammatory cy...

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