Kai Dong's research while affiliated with Beijing Jiaotong University and other places

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Publications (1)

Schematic illustration of the preparation of LdCaPd NPs.
Characterization and in vitro release studies of LdCaPd NPs. (A–C) TEM images of CaPd NPs (A), LCaPd NPs (B), and LdCaPd NPs (C), scale bars: 100 nm. (D). XRD spectra of different compositions. a. LdCaPd NPs; b. the mixture of raw materials; c. Dex; d. CaPd NPs; e. CaCl2; f. Dex. (E). In vitro release behavior of CaPd NPs in the release medium with different pH values. (F and G). In vitro release behavior of LdCaPd NPs in the release medium with different pH values, (F). Dex released from LdCaPd NPs, (G). Dsp released from LdCaPd NPs. In (E–G), **P < 0.01: significantly different from that in pH 7.4 release media. Mean ± SD, n = 3.
Cytotoxicity and cellular uptake investigation. (A) Cytotoxicity of LdCaPd NPs in RAW 264.7 (A) and HT-29 cells (B). (C) The uptake of free rhodamine B and CaPRB NPs by RAW 264.7 cells. (D). Semi-quantitative calculation results of Figure 2C. (E) The uptake of LFCaPRB NPs by RAW 264.7 cells. Green for FITC and Red for rhodamine B. (F). Semi-quantitative calculation results of Figure 2E. Scale bars: 10 μm. LPS: lipopolysaccharide, **P < 0.01, mean ± SD, n = 3.
The effect of LdCaPd NPs on macrophage polarization and inflammatory factor expression. (A). Representative fluorescence images of a cluster of differentiation CD206 (green) and nitric oxide synthase (iNOS, red) staining of unpolarized RAW 264.7 cells after being treated with different preparations. (B) Representative fluorescence images of a cluster of differentiation CD206 (green) and nitric oxide synthase (iNOS, red) staining of LPS-induced RAW 264.7 cells treated with different preparations after 12 h. (C–F). Effects of Dsp and LdCaPd NPs on cytokines expression in macrophages. (C). IL-1β; (D). TNF-α; (E). Arg-1; (F). IL-10; (G and H). NF-κB mRNA level (G) and I-κBα mRNA level (H) as determined by qRT-PCR in RAW 264.7 cells. (I). Flow cytometry analysis of the effects of Dsp and LdCaPd NPs on the phenotypic transformation of M1 and M2 macrophages. (J and K). Quantitative analysis of the effect of Dsp and LdCaPd NPs on macrophage polarization by flow cytometry. (J) M1 macrophage (%). (K) M2 macrophage (%). Scale bar: 100 µm, **P < 0.01, *P < 0.05, mean ± SD, n = 3.
In vivo distribution and pharmacokinetics behavior of LdCaPd NPs on experimental colitis mice. (A) Fluorescence distribution images in vivo and in various organs of mice. (B) Plasma concentration curves of Dsp (i.v. administration of 6 mg/kg) and LdCaPd NPs (i.v. administration of NPs containing 6 mg/kg Dsp) in rats. Mean ± SD, n = 6.

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Dexamethasone-Loaded Lipid Calcium Phosphate Nanoparticles Treat Experimental Colitis by Regulating Macrophage Polarization in Inflammatory Sites
  • Article
  • Full-text available

January 2024

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15 Reads

International Journal of Nanomedicine

International Journal of Nanomedicine

Kai Dong

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Ying Zhang

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Hong Rui Ji

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[...]

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Cui Yu You

Background The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms. Purpose A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects. Methods Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model. Results The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy. Conclusion The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.

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