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Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma.
- Source :
-
Nature communications [Nat Commun] 2022 Jul 21; Vol. 13 (1), pp. 4214. Date of Electronic Publication: 2022 Jul 21. - Publication Year :
- 2022
-
Abstract
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergistic therapy. Because our self-assembling NPs are encapsulated in membranes derived from glioma cells, they readily penetrate the blood-brain barrier and target GBM through homotypic recognition. After reaching the tumors, lactate oxidase in the NPs converts LA into pyruvic acid (PA) and hydrogen peroxide (H <subscript>2</subscript> O <subscript>2</subscript> ). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the H <subscript>2</subscript> O <subscript>2</subscript> reacts with the delivered bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate to release energy, which is used by the co-delivered photosensitizer chlorin e6 for the generation of cytotoxic singlet oxygen to kill glioma cells. Such a synergism ensures strong therapeutic effects against both glioma cell-line derived and patient-derived xenograft models.<br /> (© 2022. The Author(s).)
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 35864093
- Full Text :
- https://doi.org/10.1038/s41467-022-31799-y