TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors
| Autor: | Song, Songlin, Gui, Lin, Feng, Qiqi, Taledaohan, Ayijiang, Li, Yuanming, Wang, Wei, Wang, Yanming, Wang, Yuji |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
transmembrane peptide PAD4 inhibitor Metal Nanoparticles Antineoplastic Agents Apoptosis Arginine Histones Drug Delivery Systems Protein-Arginine Deiminase Type 4 International Journal of Nanomedicine 2-Naphthylamine Autophagy Animals Humans Original Research antitumor Mice Inbred BALB C Au nanoparticle HCT116 Cells Xenograft Model Antitumor Assays Peptide Fragments A549 Cells MCF-7 Cells tat Gene Products Human Immunodeficiency Virus Gold |
| Zdroj: | International Journal of Nanomedicine 6659–6671 |
| ISSN: | 1178-2013 |
| Popis: | Songlin Song,1,2 Lin Gui,1,2 Qiqi Feng,1,2 Ayijiang Taledaohan,1,2 Yuanming Li,3 Wei Wang,4 Yanming Wang,5 Yuji Wang1,2 1School of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People’s Republic of China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing 100069, People’s Republic of China; 3Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 4Department of Chemistry, University of Bergen, Bergen, Norway; 5School of Life Sciences, Henan University, Kaifeng 475004, People’s Republic of ChinaCorrespondence: Yuji WangSchool of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People’s Republic of ChinaTel +86 10 83950236Email wangyuji@ccmu.edu.cnPurpose: Histone citrullination by peptidylarginine deiminases 4 (PAD4) regulates the gene expression of tumor suppressor. In our previously study, YW3-56 (356) was developed as a potent PAD4 inhibitor for cancer therapy with novel function in the autophagy pathway. To enhance the antitumor activity, the PAD4 inhibitor 356 was modified by the well-established cationic penetrating peptide RKKRRQRRR (peptide TAT) and gold nanoparticles to obtain 356-TAT-AuNPs which could enhance the permeability of chemical drug in solid tumor.Methods: 356-TAT-AuNPs were prepared, and their morphology were characterized. The antitumor activity of 356-TAT-AuNPs was evaluated in vitro and in vivo.Results: 356-TAT-AuNPs exhibited higher anticancer activity against HCT-116, MCF-7 and A549 cells than 356 and 356-AuNPs. Compared with 356 and 356-AuNPs, 356-TAT-AuNPs entered the cytoplasm and nuclear, exhibited stronger anticancer activity by increasing apoptosis, inducing autophagy and inhibiting of histone H3 citrullination, and in HCT-116 xenograft mouse model, 356-TAT-AuNPs could improve the antitumor activity.Conclusion: The modified AuNPs with peptide TAT as drug delivery system are potent in delaying tumor growth and could be a powerful vehicle for profitable anticancer drug development. We believe that peptide TAT modification strategy may provide a simple and valuable method for improving antitumor activity of PAD4 inhibitors for clinical use.Keywords: Au nanoparticle, transmembrane peptide, PAD4 inhibitor, antitumor |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|