School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People's Republic of China.
Colloids Surf B Biointerfaces. 2018 Nov 1;171:485-493. doi: 10.1016/j.colsurfb.2018.07.072. Epub 2018 Jul 31.
With large surface area and three-dimensional pore structure, mesoporous carbon nanoparticles (MCN) have attracted enormous interests as potential drug carriers. However, MCN immunotoxicity has not been clarified clearly up to now. Herein we reported the effect of MCN with and without PVP or DSPE mPEG2000 (PEG) modification on immune cells including dendritic cells (DCs), T lymphocytes and RAW264.7 macrophages in vitro. Furthermore, blood biochemical tests, alexin C3 assay and histological analysis were used to investigate the toxicity of MCN in vivo. The synthesized MCN with average particle size about 90 nm was naturally insoluble in water. Surface modification with PVP (MCN-PVP) or PEG (MCN-PEG) slightly increased the particle size and Zeta potential, and effectively improved the dispersion of mesoporous carbon. MCN, MCN-PVP and MCN-PEG promoted the differentiation and maturation of the DCs, while the levels of secreted TNF-α and IL-6 were significantly suppressed by MCN-PVP and MCN-PEG. These materials significantly induced apoptosis of T lymphocytes. The histopathologic results showed that there was no significant difference between nanoparticles with or without modification. Importantly, the materials deposition was observed in the lung, which could potentially inhibit lung metastasis. In conclusion, the ordered mesoporous carbon nanoparticles superficially modified by PVP or PEG perform well in immunological biocompatibility, and are likely to be a promising candidate as medicine carrier in pharmaceutics and clinic.
具有大的表面积和三维孔结构,介孔碳纳米粒子(MCN)作为潜在的药物载体吸引了极大的兴趣。然而,MCN 的免疫毒性迄今尚未明确。本文报道了具有和不具有 PVP 或 DSPE mPEG2000(PEG)修饰的 MCN 对体外树突状细胞(DC)、T 淋巴细胞和 RAW264.7 巨噬细胞等免疫细胞的影响。此外,还进行了血液生化测试、补体 C3 测定和组织学分析,以研究 MCN 在体内的毒性。合成的 MCN 平均粒径约为 90nm,天然不溶于水。用 PVP(MCN-PVP)或 PEG(MCN-PEG)进行表面修饰略微增加了颗粒尺寸和 Zeta 电位,并有效地改善了介孔碳的分散性。MCN、MCN-PVP 和 MCN-PEG 促进了 DC 的分化和成熟,而 MCN-PVP 和 MCN-PEG 显著抑制了 TNF-α和 IL-6 的分泌。这些材料显著诱导 T 淋巴细胞凋亡。组织病理学结果表明,修饰前后的纳米颗粒没有明显差异。重要的是,观察到材料在肺中沉积,这可能潜在地抑制肺转移。总之,经 PVP 或 PEG 表面修饰的有序介孔碳纳米粒子在免疫生物相容性方面表现良好,可能成为药剂学和临床中作为药物载体的有前途的候选物。