3D Imaging and Bioengineering Laboratory, Department of Mechanical Engineering , Curtin University , Perth 6845 , Australia.
The School of Pathology and Laboratory Medicine , University of Western Australia , Perth 6009 , Australia.
ACS Appl Mater Interfaces. 2018 Apr 18;10(15):12463-12473. doi: 10.1021/acsami.8b01680. Epub 2018 Apr 6.
Utilizing nanoparticles to deliver subunit vaccines can be viewed as a promising strategy for enhancing the immune response, especially with regard to cellular immunity to fight against infectious viruses and malignant cancer. Nevertheless, its applications are still far from practicality because of some limitations such as high cost, non-biocompatibility, non-biodegradability, and the inefficient stimulation of cytotoxic T lymphocyte (CTL) response. In this study, we use metal-organic framework (MOF) MIL-101-Fe-NH nanoparticles as carriers to fabricate an innovative reduction-responsive antigen delivery system for cotransporting the antigen model ovalbumin (OVA) and an immune adjuvant, unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide. In vitro cellular tests show that the MOF nanoparticles can not only greatly improve the uptake of OVA by the antigen-presenting cells but also smartly deliver both OVA and CpG into the same cell. By feat of the reductively controllable release of OVA and the promoting function of CpG, the delivery system can elicit strong cellular immunity and CTL response in mice. Moreover, the increased frequencies of effector memory T cells inspired by the delivery system indicate that it can induce a potent immune memory response. These results demonstrate that MOF nanoparticles are excellent vehicles for codelivering antigen and immune adjuvant and may find wider applications in biomedical fields.
利用纳米颗粒传递亚单位疫苗被视为增强免疫反应的一种有前途的策略，特别是在针对传染性病毒和恶性癌症的细胞免疫方面。然而，由于成本高、生物不相容性、不可生物降解性以及细胞毒性 T 淋巴细胞（CTL）反应的低效刺激等一些限制，其应用仍远未达到实际应用的程度。在本研究中，我们使用金属有机骨架（MOF）MIL-101-Fe-NH 纳米颗粒作为载体，构建了一种创新的还原响应性抗原递药系统，用于共转运抗原模型卵清蛋白（OVA）和免疫佐剂非甲基化胞嘧啶-磷酸-鸟嘌呤（CpG）寡核苷酸。体外细胞试验表明，MOF 纳米颗粒不仅可以大大提高抗原呈递细胞对 OVA 的摄取，而且可以巧妙地将 OVA 和 CpG 递送到同一细胞中。得益于 OVA 的还原可控释放和 CpG 的促进作用，该递药系统在小鼠中引发了强烈的细胞免疫和 CTL 反应。此外，递药系统激发的效应记忆 T 细胞的频率增加表明，它可以诱导强烈的免疫记忆反应。这些结果表明，MOF 纳米颗粒是抗原和免疫佐剂共递药的理想载体，可能在生物医学领域有更广泛的应用。
