Nano spray dryer for vectorizing α-galactosylceramide in polymeric nanoparticles: A single step process to enhance invariant Natural Killer T lymphocyte responses
Nano spray dryer for vectorizing α-galactosylceramide in polymeric nanoparticles: A single step process to enhance invariant Natural Killer T lymphocyte responses
复制标题
DOI：
10.1016/j.ijpharm.2019.05.013
复制
发表时间：
2019-06-30
影响因子：
5.8
通讯作者：
Keller, Alexandre de Castro
中科院分区：
文献类型：
--
作者：
Gonzatti, Michelangelo Bauwelz;Perrud Sousa, Maria Eduarda;Keller, Alexandre de Castro
α-半乳糖神经酰胺（α GC），一种高亲和力的CD 1d抗原，由不变的自然杀伤T（iNKT）淋巴细胞识别，导致强效的免疫刺激反应，已在晚期癌症患者中使用。因此，为了提高α GC生物活性，几项研究将这种激动剂载体化在PLGA和/或PEG基纳米颗粒中。尽管有很好的发现，但这些方法需要几个步骤，从有机溶剂去污到膜系统中的挤出。使用纳米喷雾干燥器，我们在不含有机溶剂的单步过程中将α GC矢量化为阳离子共聚物（甲基丙烯酸二甲氨基乙酯、甲基丙烯酸丁酯和甲基丙烯酸甲酯- DBM）。该方法允许产生稳定的α GC-载体化纳米颗粒（DBM + α GC），其具有比游离激动剂更有效的生物活性。DBM纳米颗粒改善了体内α-GC向CD 1d分子的加载，并诱导了更高频率的IFN-γ表达iNKT细胞。因此，用DBM + aGC处理的小鼠呈现出比用游离激动剂处理的小鼠更高的血清IFN-γ水平。此外，载体化的纳米颗粒提高了α GC控制鼠肺转移癌生长的能力。因此，这是第一项研究表明，纳米喷雾干燥器技术是一种简单的替代方法，以提高iNKT反应。
The recognition of a-galactosylceramide (alpha GC), a high-affinity CD1d antigen, by the invariant Natural Killer T (iNKT) lymphocytes results in potent immunostimulatory responses that have been exploited in advanced cancer patients. Therefore, to improve alpha GC biological activity, several studies vectorized this agonist in PLGA and/or PEG-based nanoparticles. Despite promising findings, these approaches require several steps, from organic solvent decontamination through extrusion in membrane systems. Using a nano spray dryer, we vectorized alpha GC into a cationic copolymer (dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate - DBM) in a single step process, free of organic solvent. This methodology allowed the production of stable alpha GC-vectorized nanoparticles (DBM + alpha GC) with a more potent biological activity than the free agonist. DBM nanoparticles improved in vivo alpha GC loading into the CD1d molecule and induced a higher frequency of IFN-gamma-expressing iNKT cells. Consequently, mice treated with DBM + alpha GC presented higher levels of serum IFN-gamma than those treated with free agonist. Also, vectorized nanoparticles improved alpha GC ability to control the growth of murine lung metastatic carcinoma. Thus, this is the first study showing that nano spray dryer technology is a simple and alternative approach to enhance iNKT responses.