Your browser doesn't support javascript.
loading
TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors.
Song, Songlin; Gui, Lin; Feng, Qiqi; Taledaohan, Ayijiang; Li, Yuanming; Wang, Wei; Wang, Yanming; Wang, Yuji.
Afiliación
  • Song S; School of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People's Republic of China.
  • Gui L; Beijing 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.
  • Feng Q; School of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People's Republic of China.
  • Taledaohan A; Beijing 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.
  • Li Y; School of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People's Republic of China.
  • Wang W; Beijing 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.
  • Wang Y; School of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, People's Republic of China.
  • Wang Y; Beijing 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.
Int J Nanomedicine ; 15: 6659-6671, 2020.
Article en En | MEDLINE | ID: mdl-32982225
PURPOSE: 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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginina / Nanopartículas del Metal / Arginina Deiminasa Proteína-Tipo 4 / 2-Naftilamina / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Int J Nanomedicine Año: 2020 Tipo del documento: Article Pais de publicación: Nueva Zelanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arginina / Nanopartículas del Metal / Arginina Deiminasa Proteína-Tipo 4 / 2-Naftilamina / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Int J Nanomedicine Año: 2020 Tipo del documento: Article Pais de publicación: Nueva Zelanda