Created on May 12, 2022
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Tracking metastasis tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy
> Pathogenic agent's spread from an initial site to a different site within the host's body.
> Lymphatic or hematogenous spread:
circulating tumor cells acquire the ability to penetrate the walls of lymphatic or blood vessels.
> Typical for a malignant tumor.
Cascade of events:
> Tumor cell arrest on the endothelium
> Formation of dynamic contacts
> Significant cytoskeletal changes
> Tumor cell transendothelial migration
> Invasion into the surrounding matrix
Labeling tumor cells with QD
> QD was packed in cationic lipids.
> Can efficiently transduce negatively charged nucleic acids into the cytoplasm.
Intracellular labeling of tumor cells by QDs permits
in vivo imaging despite tissue autofluorescence.
Fluorescence emission spectroscopy:
> Scans the surface of a sample with an electron beam.
> High-resolution images.
IN-VIVO IMAGING :
> QDs - good multiphoton absorption between 700 - 1000 nm.
> QDs labeled with orange cell trackers were injected into the mice.
> QDs -circles; orange trackers - diamonds; lectin - squares => distinguishable from tissue autofluorescence.
> QDs - Cadmium and selenium cores.
> May cause toxicity upon prolonged stay in vivo.
> If QDs aid in extravasation/ affected the survival of the tumor cells:
Qd-labeled tumor cells in tissues < QD-labelled cells during injection.
> QD - labeled tumor cells were quantified after 40 days - no significant difference; Did not interfere with the growth of the tumor cells or cause extravasation.
> Comparison for 5 days vs 40 days - no unlabelled cells found; remained the same relatively in both cases - proof that QDs have no role in extravasation.
> Black bars: in-vitro
Grey bars: in-vivo
Multiphoton imaging of the QDs :
> Thicker tissues - absorb and scatter visible light => infrared excitation is suitable in vivo.
> Different colour emitting QDs ranging 510, 550, 570, 590, and 610 nm were identified using multiphoton emission-scanning microscopy.
> Helps identify multiple populations of cells.
> Image A: Different QDs excited at 820 nm after 5 h of injection.
> Image B: Circles - 510 nm QDs ; Diamonds -570 nm QDs;
> Image C: QDs under a coverslip excited at 680 nm.
List of sources:
Voura, E. B., Jaiswal, J. K., Mattoussi, H., & Simon, S. M. (2004). Tracking metastatic tumor cell extravasation with quantum
dot nanocrystals and fluorescence emission-scanning microscopy. Nature Medicine, 10(9), 993–998.
Peng, F., Setyawati, M. I., Tee, J. K., Ding, X., Wang, J., Nga, M. E., Ho, H. K., & Leong, D. T. (2019). Nanoparticles promote
in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness. Nature Nanotechnology, 14(3),
Chen, M. B., Whisler, J. A., Jeon, J. S., & Kamm, R. D. (2013). Mechanisms of tumor cell extravasation in an in vitro
microvascular network platform. Integrative Biology : Quantitative Biosciences from Nano to Macro, 5(10), 1262.
Cho, Hye Jin et al. “Multiphoton microscopy: an introduction to gastroenterologists.” World journal of gastroenterology vol. 17,40 (2011): 4456-60. doi:10.3748/wjg.v17.i40.4456