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Stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and verteporfin for glioblastoma therapy.
Qi, Ji; Zhang, Long; Ren, Zhongyu; Yuan, Yi; Yu, Jiahao; Zhang, Yining; Gu, Linbo; Wang, Xu; Wang, Yan; Xu, Haoyue; Yu, Rutong; Zhou, Xiuping.
Afiliación
  • Qi J; Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.
  • Zhang L; The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Ren Z; Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.
  • Yuan Y; The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Yu J; Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.
  • Zhang Y; The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Gu L; Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.
  • Wang X; The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Wang Y; Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.
  • Xu H; The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • Yu R; Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.
  • Zhou X; The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
J Nanobiotechnology ; 22(1): 495, 2024 Aug 20.
Article en En | MEDLINE | ID: mdl-39164753
ABSTRACT

BACKGROUND:

The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree.

RESULTS:

In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects.

CONCLUSION:

Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Glioblastoma / ARN Interferente Pequeño / Verteporfina / Liposomas / Ratones Desnudos Límite: Animals / Humans Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Glioblastoma / ARN Interferente Pequeño / Verteporfina / Liposomas / Ratones Desnudos Límite: Animals / Humans Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido