@article{8741272,
  abstract     = {{Impaired wound healing in people with diabetes has multifactorial causes, with insufficient neovascularization being one of the most important. Hypoxia-inducible factor-1 (HIF-1) plays a central role in the hypoxia-induced response by activating angiogenesis factors. As its activity is under precise regulatory control of prolyl-hydroxylase domain 2 (PHD-2), downregulation of PHD-2 by small interfering RNA (siRNA) could stabilize HIF-1 alpha and, therefore, upregulate the expression of pro-angiogenic factors as well. Intracellular delivery of siRNA can be achieved with nanocarriers that must fulfill several requirements, including high stability, low toxicity, and high transfection efficiency. Here, we designed and compared the performance of layer-by-layer self-assembled siRNA-loaded gold nanoparticles with two different outer layers-Chitosan (AuNP@CS) and Poly L-arginine (AuNP@PLA). Although both formulations have exactly the same core, we find that a PLA outer layer improves the endosomal escape of siRNA, and therefore, transfection efficiency, after endocytic uptake in NIH-3T3 cells. Furthermore, we found that endosomal escape of AuNP@PLA could be improved further when cells were additionally treated with desloratadine, thus outperforming commercial reagents such as Lipofectamine(R) and jetPRIME(R). AuNP@PLA in combination with desloratadine was proven to induce PHD-2 silencing in fibroblasts, allowing upregulation of pro-angiogenic pathways. This finding in an in vitro context constitutes a first step towards improving diabetic wound healing with siRNA therapy.}},
  articleno    = {{9216}},
  author       = {{Shaabani Sichani, Elnaz and Sharifiaghdam, Maryam and Lammens, Joris and De Keersmaecker, Herlinde and Vervaet, Chris and De Beer, Thomas and Motevaseli, Elahe and Ghahremani, Mohammad Hossein and Mansouri, Parvin and De Smedt, Stefaan and Raemdonck, Koen and Faridi-Majidi, Reza and Braeckmans, Kevin and Fraire, Juan}},
  issn         = {{1422-0067}},
  journal      = {{INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}},
  keywords     = {{diabetic wound healing,hypoxia,angiogenesis,cationic amphiphilic drugs,gold nanoparticles,gene delivery,layer-by-layer,INDUCIBLE FACTOR-I,PROLINE HYDROXYLATION,PULMONARY SURFACTANT,HIF-ALPHA,PROLYL,MEMBRANE,ARGININE,GROWTH,ACID,STABILIZATION}},
  language     = {{eng}},
  number       = {{17}},
  pages        = {{26}},
  title        = {{Increasing angiogenesis factors in hypoxic diabetic wound conditions by siRNA delivery : additive effect of LbL-gold nanocarriers and desloratadine-induced lysosomal escape}},
  url          = {{http://doi.org/10.3390/ijms22179216}},
  volume       = {{22}},
  year         = {{2021}},
}

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