Institute for Laser, Photonics and Biophotonics, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA.
Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Clinical Translational Research Center, The State University of New York at Buffalo, Buffalo, NY, 14203, USA.
Macromol Biosci. 2021 Jan;21(1):e2000358. doi: 10.1002/mabi.202000358. Epub 2020 Dec 7.
A nanoformulation composed of curdlan, a linear polysaccharide of 1,3-β-linked d-glucose units, hydrogen bonded to poly(γ -glutamic acid) (PGA), was developed to stimulate macrophage. Curdlan/PGA nanoparticles (C-NP) are formulated by physically blending curdlan (0.2 mg mL in 0.4 m NaOH) with PGA (0.8 mg mL ). Forster resonance energy transfer (FRET) analysis demonstrates a heterospecies interpolymer complex formed between curdlan and PGA. The H-NMR spectra display significant peak broadening as well as downfield chemical shifts of the hydroxyl proton resonances of curdlan, indicating potential intermolecular hydrogen bonding interactions. In addition, the cross peaks in H- H 2D-NOESY suggest intermolecular associations between the OH-2/OH-4 hydroxyl groups of curdlan and the carboxylic-/amide-groups of PGA via hydrogen bonding. Intracellular uptake of C-NP occurs over time in human monocyte-derived macrophage (MDM). Furthermore, C-NP nanoparticles dose-dependently increase gene expression for TNF-α, IL-6, and IL-8 at 24 h in MDM. C-NP nanoparticles also stimulate the release of IL-lβ, MCP-1, TNF-α, IL-8, IL-12p70, IL-17, IL-18, and IL-23 from MDM. Overall, this is the first demonstration of a simplistic nanoformulation formed by hydrogen bonding between curdlan and PGA that modulates cytokine gene expression and release of cytokines from MDM.
一种由线性 1,3-β 连接的 d-葡萄糖单元组成的多糖几丁质与聚（γ-谷氨酸）（PGA）通过氢键结合而成的纳米制剂被开发来刺激巨噬细胞。几丁质/PGA 纳米颗粒（C-NP）通过将几丁质（在 0.4 m NaOH 中 0.2 mg mL）与 PGA（0.8 mg mL）物理混合来制备。荧光共振能量转移（FRET）分析表明，几丁质和 PGA 之间形成了异质聚合物复合物。 1 H-NMR 光谱显示出羟基质子共振的显著峰展宽和化学位移，表明存在潜在的分子间氢键相互作用。此外， 1 H- 1 H 2D-NOESY 中的交叉峰表明，几丁质的 OH-2/OH-4 羟基与 PGA 的羧酸基/酰胺基之间通过氢键发生分子间缔合。C-NP 纳米颗粒在人单核细胞衍生的巨噬细胞（MDM）中随时间摄取。此外，C-NP 纳米颗粒在 24 小时内以剂量依赖性方式增加 MDM 中 TNF-α、IL-6 和 IL-8 的基因表达。C-NP 纳米颗粒还刺激 MDM 释放 IL-lβ、MCP-1、TNF-α、IL-8、IL-12p70、IL-17、IL-18 和 IL-23。总的来说，这是首次证明通过几丁质和 PGA 之间的氢键形成简单的纳米制剂，可调节细胞因子基因表达和 MDM 中细胞因子的释放。
