Nanoscale Zeolitic Imidazolate Framework-8 as Efficient Vehicles for Enhanced Delivery of CpG Oligodeoxynucleotides
Nanoscale Zeolitic Imidazolate Framework-8 as Efficient Vehicles for Enhanced Delivery of CpG Oligodeoxynucleotides
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DOI：
10.1021/acsami.7b09583
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发表时间：
2017-09-20
影响因子：
9.5
通讯作者：
Chen, Jinghua
中科院分区：
文献类型：
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作者：
Zhang, Huijie;Chen, Wei;Chen, Jinghua
CpG寡核苷酸(ODN)通过刺激Toll样受体9(TLR9)激活免疫系统，诱导Th1应答。因此，CpG ODN已成为治疗包括癌症、过敏和感染在内的各种疾病的免疫疗法。然而，CpG ODN的应用在很大程度上受到限制，因为它们很容易被DNA酶降解，而且细胞摄取效率低下。开发能够将CpG ODN转移到免疫细胞中的高效递送系统对于提高其治疗效果非常重要。在这里，我们首次通过将CpG ODN包裹到沸石咪唑骨架8(ZIF-8)纳米颗粒中，构建了一种新型的CpG ODN递送系统。ZIF-8分子筛的多孔结构使其具有较高的CpG ODN负载量。ZIF-8/CpG ODNS复合体在生理环境中表现出良好的稳定性，但在酸性条件下有效释放CpG ODN，与TLR9定位的内溶酶体相对应。与ZIF-8相比，ZIF-8/CpG ODNS复合体无细胞毒性。ZIF-8显著增加RAW264.7细胞对CpG ODN的摄取，从而进一步促进体内和体外免疫细胞因子的分泌。我们的结果表明，纳米级金属有机骨架(MOF)可以作为理想的载体来传递CpG ODN。
CpG oligodeoxynucleotides (ODNs) activate the immune system and induce Th 1 responses by stimulation of Toll-like receptor 9 (TLR9). Thus, CpG ODNs have become immunotherapeutics against various diseases including cancers, allergies, and infection. However, applications of CpG ODNs are largely zny limited because of their easy degradation by DNase as well as inefficient cellular uptake. Development of efficient delivery systems capable of transferring CpG ODNs into immune cells is important to enhance their therapeutic efficacy. Herein, for the first time, we demonstrated the construction of a novel CpG ODNs delivery system by encapsulating CpG ODNs into zeolitic imidazolate framework 8 (ZIF-8) nanoparticles. ZIF-8 possessed high CpG ODNs loading capacity due to its porous structure. ZIF-8/CpG ODNs complexes exhibited good stability in a physiological environment but effectively released CpG ODNs in acid conditions corresponding to the TLR 9-localized endolysosomes. ZIF-8/CpG ODNs complexes had no cytotoxicity in contrast to ZIF-8. ZIF-8 significantly increased the intracellular uptake of CpG ODNs in RAW264.7 cells, which further enhanced the secretion of immune cytokines both in vitro and in vivo. Our results suggest that nanoscale metal organic frameworks (MOFs) can serve as ideal vehicles for the delivery of CpG ODNs.