靶向SERPINE1的工程纳米囊泡克服了胶质母细胞瘤对替莫唑胺的耐药性。

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-03-24 DOI:10.1016/j.cellsig.2025.111763

Jianping Wen , Dongxu Wu , Yi Le , Zonghua Yin , Minglong Chen , Yulong Shen , Xia Wu , Kebo Liu , Kun Luo , Zhicheng Shu , Qingxia Shu , Dongsheng Ouyang

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引用次数: 0

摘要

多形性胶质母细胞瘤（GBM）是一种高度侵袭性的脑肿瘤，由于其对替莫唑胺（TMZ）的耐药性，治疗选择有限。本研究探索了一种新的治疗方法，利用负载SERPINE1抑制剂的工程细胞膜纳米囊泡来对抗TMZ耐药性。高通量测序确定了与耐药性相关的关键基因，而纳米囊泡表现出优异的稳定性和穿越血脑屏障的能力。功能分析显示，其显著抑制GBM细胞活力、迁移和侵袭，并伴有SERPINE1和VEGF的表达降低，表明其抑制了血管生成和肿瘤进展。这些发现突出了serpine1靶向纳米囊泡作为克服GBM中TMZ耐药性的创新和有效策略的潜力。

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Engineered nanovesicles targeting SERPINE1 overcome temozolomide resistance in glioblastoma

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with limited treatment options due to its resistance to temozolomide (TMZ). This study explores a novel therapeutic approach using engineered cell membrane nanovesicles loaded with SERPINE1 inhibitors to combat TMZ resistance. High-throughput sequencing identified pivotal genes associated with resistance, while the nanovesicles demonstrated excellent stability and the ability to cross the blood-brain barrier. Functional assays revealed significant suppression of GBM cell viability, migration, and invasion, accompanied by reduced expression of SERPINE1 and VEGF, suggesting inhibition of angiogenesis and tumor progression. These findings highlight the potential of SERPINE1-targeted nanovesicles as an innovative and effective strategy for overcoming TMZ resistance in GBM.

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.