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PARP inhibitor boost the efficacy of photothermal therapy to TNBC through enhanced DNA damage and inhibited homologous recombination repair.
Li, Yang; Miao, Wenfang; Yuan, Chen; Tang, Jiajia; Zhong, Nan; Jin, Yingying; Hu, Yongzhi; Tang, Yuxia; Wang, Shouju.
Afiliación
  • Li Y; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China.
  • Miao W; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China.
  • Yuan C; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China.
  • Tang J; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China.
  • Zhong N; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China.
  • Jin Y; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China.
  • Hu Y; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China.
  • Tang Y; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China.
  • Wang S; Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhoulu, Nanjing, Jiangsu, China. shouju.wang@gmail.com.
Drug Deliv Transl Res ; 2024 Jul 02.
Article en En | MEDLINE | ID: mdl-38954244
ABSTRACT
Triple-negative breast cancer (TNBC) could benefit from PARP inhibitors (PARPi) for their frequent defective homologous recombination repair (HR). However, the efficacy of PARPi is limited by their lower bioavailability and high susceptibility to drug resistance, so it often needs to be combined with other treatments. Herein, polydopamine nanoparticles (PDMN) were constructed to load Olaparib (AZD) as two-channel therapeutic nanoplatforms. The PDMN has a homogeneous spherical structure around 100 nm and exhibits a good photothermal conversion efficiency of 62.4%. The obtained AZD-loaded nanoplatform (PDMN-AZD) showed enhanced antitumor effects through the combination of photothermal therapy (PTT) and PARPi. By western blot and flow cytometry, we found that PTT and PARPi could exert synergistic antitumor effects by further increasing DNA double-strand damage (DSBs) and enhancing HR defects. The strongest therapeutic effect of PDMN-AZD was observed in a BRCA-deficient mouse tumor model. In conclusion, the PDMN-AZD nanoplatform designed in this study demonstrated the effectiveness of PTT and PARPi for synergistic treatment of TNBC and preliminarily explained the mechanism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Drug Deliv Transl Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Drug Deliv Transl Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos