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Co-culture of Glioblastoma Stem-like Cells on Patterned Neurons to Study Migration and Cellular Interactions
Published on: February 24, 2021
Real-time visualization of nanoparticles interacting with glioblastoma stem cells
Elliot S Pohlmann1,2, Kaya Patel1, Sujuan Guo1
1†Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, Virginia 24016, United States.
Abstract:
Nanoparticle-based therapy represents a novel and promising approach to treat glioblastoma, the most common and lethal malignant brain cancer. Although similar therapies have achieved significant cytotoxicity in cultured glioblastoma or glioblastoma stem cells (GSCs), the lack of an appropriate approach to monitor interactions between cells and nanoparticle-based therapies impedes their further clinical application in human patients. To address this critical issue, we first obtained NOTCH1 positive GSCs from patient-derived primary cultures. We then developed a new imaging approach to directly observe the dynamic nature of nanoparticles at the molecular level using in situ transmission electron microscopy (TEM). Utilizing these tools we were able to visualize real-time movements of nanoparticles interacting with GSCs for the first time. Overall, we show strong proof-of-concept results that real-time visualization of nanoparticles in single cells can be achieved at the nanoscale using TEM, thereby providing a powerful platform for the development of nanotherapeutics.
Insights
This study introduces a new imaging method using transmission electron microscopy (TEM) to visualize nanoparticle interactions with glioblastoma stem cells (GSCs) in real-time. This breakthrough enables nanoscale observation, advancing nanotherapeutic development for brain cancer.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Nanotechnology
Background:
- Glioblastoma is a lethal brain cancer with limited treatment options.
- Nanoparticle-based therapies show promise but lack real-time monitoring methods.
- Glioblastoma stem cells (GSCs) are crucial targets for effective treatment.
Purpose of the Study:
- To develop and validate a novel imaging approach for observing nanoparticle-GSC interactions.
- To enable real-time, molecular-level visualization of nanotherapeutics within GSCs.
- To provide a platform for advancing nanoparticle-based glioblastoma treatment.
Main Methods:
- Isolated NOTCH1 positive GSCs from patient-derived primary cultures.
- Developed an in situ transmission electron microscopy (TEM) imaging technique.
- Visualized dynamic nanoparticle interactions with GSCs at the nanoscale.
Main Results:
- Successfully visualized real-time movements of nanoparticles interacting with GSCs.
- Demonstrated the capability of TEM for nanoscale observation of cellular-nanoparticle dynamics.
- Established a proof-of-concept for real-time visualization of nanotherapeutics in single cells.
Conclusions:
- In situ TEM provides a powerful tool for observing nanoparticle-GSC interactions.
- Real-time nanoscale visualization is critical for developing effective nanotherapeutics.
- This approach facilitates the advancement of nanoparticle-based glioblastoma treatments.

