1. Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma.
- Author
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Lu G, Wang X, Li F, Wang S, Zhao J, Wang J, Liu J, Lyu C, Ye P, Tan H, Li W, Ma G, and Wei W
- Subjects
- Biomimetics, Cell Line, Tumor, Humans, Hydrogen Peroxide, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Glioblastoma drug therapy, Glioblastoma pathology, Glioma, Nanoparticles
- 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
2 O2 ). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the H2 O2 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., (© 2022. The Author(s).)- Published
- 2022
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