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Hybrid Curdlan Poly(γ ‐Glutamic Acid) Nanoassembly for Immune Modulation in Macrophage
Author(s) -
Heo Jeongyun,
Sobiech Thomas A.,
Kutscher Hilliard L.,
Chaves Lee,
Sukumaran Dinesh K.,
Karki Shanta,
Dube Admire,
Prasad Paras N.,
Reynolds Jessica L.
Publication year - 2021
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.202000358
Subject(s) - curdlan , chemistry , hydrogen bond , amide , stereochemistry , biophysics , glutamic acid , polysaccharide , biochemistry , organic chemistry , amino acid , molecule , biology
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 −1 in 0.4 m NaOH) with PGA (0.8 mg mL −1 ). Forster resonance energy transfer (FRET) analysis demonstrates a heterospecies interpolymer complex formed between curdlan and PGA. The 1 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 1 H‐ 1 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.