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Advancing Targeted Drug Delivery in Glioblastoma Multiforme Through Biomimetic Nanomedicine Using 3D Tumor-On-a-Chip
Twinkle Jina Minette Manoharan1, Ting-Yun Wang1,2, Shivani Mantri1
1School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA.
Advanced Healthcare Materials
|September 8, 2025
Summary
A novel tumor-on-a-chip platform enhances drug delivery to glioma stem cells (GSCs) in glioblastoma (GBM). Monocyte-coated nanoparticles carrying verteporfin effectively inhibited GSC growth, offering new therapeutic strategies for GBM.
Area of Science:
- Oncology
- Biotechnology
- Nanomedicine
Background:
- Glioblastoma multiforme (GBM) has a poor prognosis due to persistent glioma stem cells (GSCs) in the protective perivascular niche (PVN).
- The tumor microenvironment (TME) and its vasculature present challenges for drug penetration and effective treatment.
- Existing preclinical models lack the complexity to accurately represent the human TME and GSC niche interactions.
Purpose of the Study:
- To engineer an innovative 3D ex-vivo tumor-on-a-chip (TOC) platform replicating the GBM perivascular niche (PVN).
- To evaluate the efficacy of monocyte membrane-coated nanoparticles (MoNP) for targeted drug delivery to GSCs within the PVN.
- To assess the therapeutic potential of verteporfin delivered via MoNP in inhibiting GSC growth and invasiveness.
Main Methods:
- Development of a 3D ex-vivo tumor-on-a-chip (TOC) platform to model the perivascular niche (PVN).
- Utilizing monocyte membrane-coated nanoparticles (MoNP) for targeted delivery of verteporfin to glioma stem cells (GSCs).
- Employing transcriptomic profiling and cytokine analysis to assess therapeutic effects and validate the model.
Main Results:
- The TOC platform accurately replicated the structural and functional characteristics of the PVN.
- MoNP effectively targeted abnormal tumor microvasculature, enhancing drug delivery to GSCs.
- MoNP-delivered verteporfin significantly inhibited GSC growth and invasiveness, unlike free-form verteporfin.
- Transcriptomic and cytokine analyses confirmed MoNP-mediated verteporfin delivery modulated key tumor-related pathways.
Conclusions:
- The integrated TOC-MoNP platform provides a clinically relevant model for studying glioblastoma (GBM) and developing therapies.
- Targeted delivery of verteporfin using MoNP is a promising strategy to overcome drug penetration challenges in the GBM TME.
- This approach offers new opportunities for more effective glioblastoma treatment by targeting persistent glioma stem cells.

