Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, India.
Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai, 600 036, India.
Mater Sci Eng C Mater Biol Appl. 2020 Mar;108:110379. doi: 10.1016/j.msec.2019.110379. Epub 2019 Nov 3.
Curdlan, an insoluble and neutral polysaccharide, was produced from Agrobacterium sp. ATCC 31750 and chemically modified with dimethylaminoethyl (DMAE) group to introduce gene binding ability. The resulting DMAE-curdlan was crosslinked with curdlan nanoparticles using epichlorohydrin. The prepared nanoparticles are spherical with an average diameter of 523 ± 195 nm, stable and are highly biocompatible with differentiated THP-1 macrophages with viability of above 90%. They are taken up more efficiently by RAW 264.7 macrophage cells than by L929 fibroblast cells. They increase the expression of M1 macrophage marker genes, TNFα and CXCL10, and decrease the expression of M2 marker, CD206, indicating their ability to activate M1 phenotype and aid in tumor regression. They are also capable of delivering siRNA to human macrophage-like cells efficiently and inhibit ~59% of the expression of target MMP-9 protein. These results indicate that this modified curdlan-based nanoparticle is a promising vehicle for the delivery of siRNAs to macrophages, which could open up treatment strategies for a range of diseases.
由农杆菌属 ATCC 31750 产生的不溶性中性多糖几丁质聚糖经二甲氨基乙基（DMAE）基团化学修饰，引入基因结合能力。所得的 DMAE-几丁质聚糖用表氯醇与几丁质纳米颗粒交联。所制备的纳米颗粒呈球形，平均直径为 523 ± 195nm，稳定，与分化的 THP-1 巨噬细胞高度相容，细胞活力超过 90%。与 L929 成纤维细胞相比，它们被 RAW 264.7 巨噬细胞摄取的效率更高。它们增加了 M1 巨噬细胞标记基因 TNFα 和 CXCL10 的表达，降低了 M2 标记物 CD206 的表达，表明它们具有激活 M1 表型和帮助肿瘤消退的能力。它们还能够有效地将 siRNA 递送至人巨噬细胞样细胞，并抑制 MMP-9 靶蛋白表达约 59%。这些结果表明，这种经过修饰的基于几丁质聚糖的纳米颗粒是向巨噬细胞递送 siRNA 的有前途的载体，可为一系列疾病的治疗策略开辟新的途径。
