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NGR-modified PEG-PLGA Micelles Containing Shikonin Enhance Targeting of Dendritic Cells for Therapy of Allergic Rhinitis
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  • Chengcheng Liu,
  • Wenwen Qi,
  • Zhenxiao Teng,
  • Runtong Xu,
  • Yue Xi,
  • Yiming Qin,
  • Xinhao Wu,
  • Fangyuan Zhu,
  • Fenglei Xu,
  • Lei Shi,
  • Miaoqing Zhao,
  • Ming Xia
Chengcheng Liu
Shandong Provincial Hospital
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Wenwen Qi
Shandong Provincial Hospital
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Zhenxiao Teng
Shandong Provincial Hospital
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Runtong Xu
Shandong Provincial Hospital
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Yue Xi
Shandong Provincial Hospital
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Yiming Qin
Shandong Normal University
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Xinhao Wu
Shandong Provincial Hospital
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Fangyuan Zhu
Shandong Provincial Hospital
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Fenglei Xu
Shandong Provincial Hospital
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Lei Shi
Shandong Provincial Hospital
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Miaoqing Zhao
Shandong Provincial Hospital
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Ming Xia
Shandong Provincial Hospital

Corresponding Author:[email protected]

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Abstract

Background: Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa related with Th2 lymphocyte. Dendritic cells (DCs) have been considered to play an important role in the development and maintenance of AR. But the particular therapies specifically targeting DC are still lacking in clinic. Shikonin (SHI) is a natural naphthoquinone compound isolated from the Chinese herb Radix Arnebiae. It is reported that SHI can inhibit the phenotype and function of DCs, so we speculate that SHI may be an effective drug for the treatment of AR. However, the clinical usage of SHI has been limited by the bioactive properties of poor solubility, short retention time and low bioavailability. Therefore, in order to better exert the anti-inflammatory effect of SHI, an efficient SHI delivery system is urgently needed. Methods: we prepared and characterized SHI-PM and NGR-SHI-PM with the thin-film hydration method. Retrodialysis method was employed to determine the release behavior. We took immunofluorescence to investigate the expression of CD13 in vitro. Then we tested BM-DCs mature cell detection by flow cytometry. An allergic rhinosinusitis murine model, hematoxylin and eosin stain and flow cytometry were established to detect the anti-inflammatory efficiency in vivo. At last, western blot analysis and plasmid construction and transfection assay were taken to reveal the molecular mechanisms. Results: In the present study, we revealed that NGR-modifified could strengthen the intracellular uptake of PM and CD13 was high expressed on mature BM-DCs. NGR-modified could enhance the inhibition of SHI in vitro. NGR-modifified could increase the distribution of PM in vivo by DiI fluorescently. NGR-modified could enhance SHI anti-allergic activity in OVA-sensitized mice and enhance the inhibition of SHI on DC maturation in lymph node. Our findings also suggest that SHI may have the inhibitory effect on AR through NF-κB pathway by targeting PARP. Conclusions: In summary, we have shown that NGR-PM-SHI may provide a promising platform for improving targeted therapy AR both in vitro and in vivo through the NF-κB pathway by targeting PARP and could be a novel strategy for treating allergic rhinitis.