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工程仿生纳米颗粒实现了针对脑胶质瘤的靶向递送和基于代谢的高效协同治疗。

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

机构信息

Department of Neurosurgery, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518035, P. R. China.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

出版信息

Nat Commun. 2022 Jul 21;13(1):4214. doi: 10.1038/s41467-022-31799-y.

DOI:10.1038/s41467-022-31799-y
PMID:35864093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9304377/
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 (HO). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the HO 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.

摘要

多形性胶质母细胞瘤（GBM）是一种侵袭性脑癌，预后较差，治疗选择有限。在这里，我们基于对切除的 GBM 中乳酸（LA）升高的观察，开发了仿生治疗纳米颗粒（NPs），这些 NPs 可提供基于 LA 代谢的协同治疗药物。由于我们的自组装 NPs 被包裹在源自神经胶质瘤细胞的膜中，因此它们可以轻易穿透血脑屏障，并通过同型识别靶向 GBM。到达肿瘤后，NPs 中的乳酸氧化酶将 LA 转化为丙酮酸（PA）和过氧化氢（HO）。PA 通过阻断组蛋白表达和诱导细胞周期停滞来抑制癌细胞生长。同时，HO 与递送的双[2,4,5-三氯-6-（戊氧基羰基）苯基]草酸酯反应，释放能量，供共递送的光敏剂氯代 E6 用于生成细胞毒性单线态氧以杀死神经胶质瘤细胞。这种协同作用确保了对源自神经胶质瘤细胞系和患者来源异种移植模型的强烈治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/b1616129bd2a/41467_2022_31799_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/68e24a83d319/41467_2022_31799_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/ac6b286367b9/41467_2022_31799_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/d047e4029be7/41467_2022_31799_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/d2b6acd403bd/41467_2022_31799_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/856a6c744459/41467_2022_31799_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/0226cb0e8f56/41467_2022_31799_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/b42288c49504/41467_2022_31799_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/b1616129bd2a/41467_2022_31799_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/68e24a83d319/41467_2022_31799_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/ac6b286367b9/41467_2022_31799_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/d047e4029be7/41467_2022_31799_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/d2b6acd403bd/41467_2022_31799_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/856a6c744459/41467_2022_31799_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/0226cb0e8f56/41467_2022_31799_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/b42288c49504/41467_2022_31799_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a9/9304377/b1616129bd2a/41467_2022_31799_Fig8_HTML.jpg

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