Journal
NANO LETTERS
Volume 15, Issue 4, Pages 2329-2335Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nl504481k
Keywords
Glioblastoma stem cells; in situ transmission electron microscopy; gold nanoparticles; nanorods; NOTCH1 receptor; microfluidics
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Funding
- Virginia Tech Carilion School of Medicine and Research Institute
- Institute for Critical Technology and Applied Science (ICTAS) at Virginia Tech
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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.
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