Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma

Guihong Lu, Xiaojun Wang, Feng Li, Shuang Wang, Jiawei Zhao, Jinyi Wang, Jing Liu, Chengliang Lyu, Peng Ye, Hui Tan (), Weiping Li (), Guanghui Ma () and Wei Wei ()
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Guihong Lu: The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital
Xiaojun Wang: Chinese Academy of Sciences
Feng Li: Chinese Academy of Sciences
Shuang Wang: Chinese Academy of Sciences
Jiawei Zhao: Chinese Academy of Sciences
Jinyi Wang: The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital
Jing Liu: The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital
Chengliang Lyu: Chinese Academy of Sciences
Peng Ye: Chinese Academy of Sciences
Hui Tan: The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital
Weiping Li: The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital
Guanghui Ma: Chinese Academy of Sciences
Wei Wei: Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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 (H2O2). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the H2O2 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.

Date: 2022
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DOI: 10.1038/s41467-022-31799-y

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