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

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

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-M...

Full description

Saved in:
Bibliographic Details
Main Authors: Zahra Shokri Varniab, Edwin Chang, Jie Wang, Ramesh Duwa, Vidyani Suryadevara, Wei Wu, Manoj Kumar, Tie Liang, Zubeda Khatoon, Goreti Ribeiro Morais, Robert Falconer, Yifeng Shi, Grigory Tikhomirov, Kerem Nernekli, Laura Jean Pisani, Heike Elisabeth Daldrup-Link
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
Glioblastoma
Theranostic
Nanoparticles
MRI
Ferumoxytol
Online Access:https://doi.org/10.1038/s41598-025-97775-w
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322

Similar Items