Evidence map›Paper›PMID 42035162›Full record

ArticleJournal of nanobiotechnology2026

Overcoming blood-brain barrier and chemoresistance in glioblastoma by Angiopep-2-modified NK cell-derived extracellular vesicles for targeted delivery of temozolomide.

Jun Liu, Wenjin Wei, Qianliang Huang, Ying Gong, Bangming Guo, Zhe Zhang, Yancong Yang, Shuaishuai Xue, Yonghua Cai, Zhengming Zhan and 5 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Jun Liu *Department of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Wenjin Wei *Department of Neurosurgery, Ganzhou People's Hospital, Ganzhou, 341000, Jiangxi, China.
Qianliang Huang *Department of Neurosurgery, Ganzhou People's Hospital, Ganzhou, 341000, Jiangxi, China.
Ying Gong *Department of Laboratory Medicine, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, Guangdong, China.
Bangming GuoDepartment of Neurosurgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, China.
Zhe ZhangDepartment of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Yancong YangDepartment of Neurosurgery, Ganzhou People's Hospital, Ganzhou, 341000, Jiangxi, China.
Shuaishuai XueDepartment of Neurosurgery, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, Guangdong, China.
Yonghua CaiDepartment of Neurosurgery, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, Guangdong, China.
Zhengming ZhanDepartment of Neurosurgery, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, Guangdong, China.
Peng LiDepartment of Neurosurgery, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, Guangdong, China.
Qiuhua JiangDepartment of Neurosurgery, Ganzhou People's Hospital, Ganzhou, 341000, Jiangxi, China.
Xinyun YeDepartment of Neurosurgery, Ganzhou People's Hospital, Ganzhou, 341000, Jiangxi, China. yexinyun1270@163.com.
Ye SongDepartment of Neurosurgery, Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, China. songye@smu.edu.cn.
Hua GuoDepartment of Neurosurgery, the 2nd affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China. ndefy02014@ncu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM) remains incurable due to the blood-brain barrier (BBB) limiting drug delivery and intrinsic/acquired resistance to temozolomide (TMZ), the first-line chemotherapy. Here, we developed Angiopep-2 (Ang)-modified natural killer cell-derived extracellular vesicles (Ang-NK-EV) for targeted TMZ delivery (Ang-NK-EV@TMZ) to address these bottlenecks. NK-EV were prepared via freeze-thaw extrusion of NK-92 cells, loaded with TMZ, and surface-functionalized with Ang to target LRP1 (highly expressed at the BBB and on GBM cells). Characterization confirmed Ang-NK-EV@TMZ exhibited spherical morphology, preserved EV markers (TSG101, CD9/63/81), and retained NK cell-derived immune factors (IFN-γ, GZMB). In vitro, Ang modification enhanced GBM cell uptake (2.5-3.2-fold vs. NK-EV) and BBB transcytosis (2.8-3.5-fold vs. free TMZ). Ang-NK-EV@TMZ reversed TMZ resistance by modulating STING/ mTOR/ MGMT signaling (via IFN-γ) and inducing apoptosis (elevated cleaved caspase-3, γ-H2AX). It also triggered immunogenic cell death (increased ATP, HMGB1) and polarized macrophages to M1-like phenotypes. In orthotropic GBM models, Ang-NK-EV@TMZ accumulated in brain tumors, inhibited growth (7.2-fold lower bioluminescence vs. PBS), and extended median survival (42 days vs. 18 days for PBS). No significant organ toxicity or hemolysis was observed. This platform integrates targeted chemotherapy and immune modulation, highlighting NK-EV' potential for GBM therapy.

Indexed as

Blood-Brain BarrierDrug Resistance, NeoplasmExtracellular VesiclesGlioblastomaKiller Cells, NaturalTemozolomideAnimalsApoptosisBrain NeoplasmsCell Line, TumorDrug Delivery SystemsHumansPeptidesAngiopep-2PeptidesTemozolomideAngiopep-2 (Ang)Blood-brain barrier (BBB)ChemoresistanceGlioblastoma (GBM)NK cell-derived extracellular vesicles (NK-EV)STING/mTOR/MGMT signalingTemozolomide (TMZ)Tumor immune microenvironment (TME)

Identifiers

PMID42035162
PMCPMC13353015

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.