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Efficient Delivery of Lomitapide using Hybrid Membrane-Coated Tetrahedral DNA Nanostructures for Glioblastoma Therapy.
- Source :
-
Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2024 Jun; Vol. 36 (24), pp. e2311760. Date of Electronic Publication: 2024 Apr 11. - Publication Year :
- 2024
-
Abstract
- Glioblastoma (GBM) is the most aggressive and prevalent primary malignant tumor of the central nervous system. Traditional chemotherapy has poor therapeutic effects and significant side effects due to drug resistance, the natural blood-brain barrier (BBB), and nonspecific distribution, leading to a lack of clinically effective therapeutic drugs. Here, 1430 small molecule compounds are screened based on a high-throughput drug screening platform and a novel anti-GBM drug, lomitapide (LMP) is obtained. Furthermore, a bionic nanodrug delivery system (RFA NPs) actively targeting GBM is constructed, which mainly consists of tetrahedral DNA nanocages (tFNA NPs) loaded with LMP as the core and a folate-modified erythrocyte-cancer cell-macrophage hybrid membrane (FRUR) as the shell. FRUR camouflage conferred unique features on tFNA NPs, including excellent biocompatibility, improved pharmacokinetic profile, efficient BBB permeability, and tumor targeting ability. The results show that the LMP RFA NPs exhibited superior and specific anti-GBM activities, reduced off-target drug delivery, prolonged lifespan, and has negligible side effects in tumor-bearing mice. This study combines high-throughput drug screening with biomimetic nanodrug delivery system technology to provide a theoretical and practical basis for drug development and the optimization of clinical treatment strategies for GBM treatment.<br /> (© 2024 Wiley‐VCH GmbH.)
- Subjects :
- Animals
Mice
Humans
Cell Line, Tumor
Blood-Brain Barrier metabolism
Nanostructures chemistry
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Drug Carriers chemistry
Benzimidazoles chemistry
Brain Neoplasms drug therapy
Brain Neoplasms pathology
Glioblastoma drug therapy
Glioblastoma pathology
Glioblastoma metabolism
DNA chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4095
- Volume :
- 36
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Advanced materials (Deerfield Beach, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 38569065
- Full Text :
- https://doi.org/10.1002/adma.202311760