Evidence map›Paper›PMID 40253484›Full record

ArticleScientific reports2025

Dual-enzyme activated theranostic nanoparticles for image-guided glioblastoma therapy.

Zahra Shokri Varniab, Edwin Chang, Jie Wang, Ramesh Duwa, Vidyani Suryadevara, Wei Wu, Manoj Kumar, Tie Liang, Zubeda Khatoon, Goreti Ribeiro Morais and 6 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Zahra Shokri VarniabDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Edwin ChangDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Jie WangDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Ramesh DuwaDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Vidyani SuryadevaraDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Wei WuDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Manoj KumarDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Tie LiangDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Zubeda KhatoonFaculty of Life Sciences, Institute of Cancer Therapeutics, University of Bradford, Bradford, UK.
Goreti Ribeiro MoraisFaculty of Life Sciences, Institute of Cancer Therapeutics, University of Bradford, Bradford, UK.
Robert FalconerFaculty of Life Sciences, Institute of Cancer Therapeutics, University of Bradford, Bradford, UK.
Yifeng ShiDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, USA.
Grigory TikhomirovDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, USA.
Kerem NernekliDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Laura Jean PisaniDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA.
Heike Elisabeth Daldrup-LinkDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, 725 Welch Rd, Stanford, CA, 94305-5614, USA. heiked@stanford.edu.

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Melinda L. Telli · 2007 to 2026
$71.4M
Theranostics for Pediatric Brain CancerR01HD103638 · NICHD · STANFORD UNIVERSITY · PI DALDRUP-LINK, HEIKE ELIZABETH · 2021 to 2025
$3.3M
Upgrade of the Stanford GE-Varian Experimental MRI Scanner to the Current Model MS10RR026917 · NCRR · STANFORD UNIVERSITY · PI MOSELEY, MICHAEL E · 2010 to 2010
$497k
NCI NIH HHS P30 CA124435NCRR NIH HHS S10 RR026917NICHD NIH HHS R01 HD103638
6 · The paper itself

Abstract

Matrix metalloproteinase-14 (MMP-14) and Cathepsin-B (Cat-B) are overexpressed in glioblastoma (GBM) and not normal brain, making them promising targets for prodrug activation. We investigated a novel combination therapy using two tumor-enzyme activatable theranostic nanoprobes (TNP): TNP-MMP-14, which disrupts the blood tumor barrier via MMP-14 activation, and TNP-Cat-B, which selectively targets GBM cells through Cat-B activation. We hypothesized that combining TNP-MMP-14 and TNP-Cat-B would enhance TNP tumor accumulation and therapeutic efficacy compared to TNP-Cat-B monotherapy. Thirty NSG mice with luciferase-expressing GBM39 tumors received either TNP-MMP-14 plus TNP-Cat-B, TNP-Cat-B only, or saline. Magnetic resonance imaging (MRI) was conducted pre- and post-treatment, with T2* relaxation times analyzed using a generalized linear model. Histopathological differences were assessed using Kruskal-Wallis and Mann-Whitney tests. A Bonferroni correction was applied to account for multiple comparisons. Combination therapy significantly reduced tumor T2* relaxation times (12.98 ± 4.20 ms) compared to TNP-Cat-B monotherapy (22.49 ± 3.95 ms, p < 0.001). The apoptotic marker caspase-3 was also significantly higher in the combination group (64.46 ± 23.43 vs. 15.93 ± 5.81, p < 0.001). These findings demonstrate the potential of dual-enzyme activatable nanoparticles to enhance GBM treatment by overcoming drug delivery barriers and improving therapeutic efficacy over monotherapy.

Indexed as

Brain NeoplasmsCathepsin BGlioblastomaMatrix Metalloproteinase 14NanoparticlesTheranostic NanomedicineAnimalsCell Line, TumorHumansMagnetic Resonance ImagingMiceProdrugsXenograft Model Antitumor AssaysCathepsin BMatrix Metalloproteinase 14ProdrugsFerumoxytolGlioblastomaMRINanoparticlesTheranostic

Identifiers

PMID40253484
PMCPMC12009400

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.