Protein Toxin Chaperoned by LRP-1-Targeted Virus-Mimicking Vesicles Induces High-Efficiency Glioblastoma Therapy In Vivo

Protein Toxin Chaperoned by LRP-1-Targeted Virus-Mimicking Vesicles Induces High-Efficiency Glioblastoma Therapy In Vivo

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 30(2018), 30 vom: 03. Juli, Seite e1800316
1. Verfasser: Jiang, Yu (VerfasserIn)
Weitere Verfasser: Yang, Weijing, Zhang, Jian, Meng, Fenghua, Zhong, Zhiyuan
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article angiopep-2 blood-brain barrier glioblastoma polymersomes therapeutic proteins
Beschreibung
Zusammenfassung:© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Glioblastoma is a most intractable and high-mortality malignancy because of its extremely low drug accessibility resulting from the blood-brain barrier (BBB). Here, it is reported that angiopep-2-directed and redox-responsive virus-mimicking polymersomes (ANG-PS) (angiopep-2 is a peptide targeting to low-density lipoprotein receptor-related protein-1 (LRP-1)) can efficiently and selectively chaperone saporin (SAP), a highly potent natural protein toxin, to orthotopic human glioblastoma xenografts in nude mice. Unlike chemotherapeutics, free SAP has a low cytotoxicity. SAP-loaded ANG-PS displays, however, a striking antitumor activity (half-maximal inhibitory concentration, IC50  = 30.2 × 10-9 m) toward U-87 MG human glioblastoma cells in vitro as well as high BBB transcytosis and glioblastoma accumulation in vivo. The systemic administration of SAP-loaded ANG-PS to U-87 MG orthotopic human-glioblastoma-bearing mice brings about little side effects, effective tumor inhibition, and significantly improved survival rate. The protein toxins chaperoned by LRP-1-targeted virus-mimicking vesicles emerge as a novel and highly promising treatment modality for glioblastoma
Beschreibung:Date Completed 07.03.2019
Date Revised 09.01.2021
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.201800316