Real-time visualization of nanoparticles interacting with glioblastoma stem cells.
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.
†Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, Virginia 24016, United States.|‡Virginia Tech Carilion School of Medicine, 2 Riverside Circle, Roanoke, Virginia 24016, United States.
Elliot S
ES
Pohlmann
†Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, Virginia 24016, United States.
Kaya
K
Patel
†Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, Virginia 24016, United States.
Sujuan
S
Guo
§Protochips, Inc., Applications Science, 616 Hutton Street, Raleigh, North Carolina 27606, United States.
Madeline J
MJ
Dukes
†Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, Virginia 24016, United States.|‡Virginia Tech Carilion School of Medicine, 2 Riverside Circle, Roanoke, Virginia 24016, United States.|∥Department of Biomedical Sciences and Pathology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia 24061, United States.|#Faculty of Health Sciences, Virginia Tech, Blacksburg, Virginia 24061, United States.
Zhi
Z
Sheng
†Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, Virginia 24016, United States.|‡Virginia Tech Carilion School of Medicine, 2 Riverside Circle, Roanoke, Virginia 24016, United States.|⊥Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia 24061, United States.|#Faculty of Health Sciences, Virginia Tech, Blacksburg, Virginia 24061, United States.
Deborah F
DF
Kelly
D045744:Cell Line, Tumor; D003199:Computer Systems; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005909:Glioblastoma / Q000737:chemistry / Q000648:ultrastructure*; D006801:Humans; D007089:Image Enhancement / Q000295:instrumentation; D056656:Lab-On-A-Chip Devices; D046529:Microscopy, Electron, Transmission / Q000295:instrumentation*; D057054:Molecular Imaging / Q000295:instrumentation*; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure*; D014411:Neoplastic Stem Cells / Q000737:chemistry* / Q000648:ultrastructure
Glioblastoma stem cells; NOTCH1 receptor; gold nanoparticles; in situ transmission electron microscopy; microfluidics; nanorods