Microscopy has become an increasingly sophisticated and essential tool for scientists who want to visualize cellular structures with precision. One microscopy technique that exemplifies this increased level of sophistication is nonlinear optical microscopy (NOLM), which enables the creation of high contrast three-dimensional images of cells and tissues.
NOLM has proven particularly useful for imaging the interface between two different materials—for example, where the cell membrane comes in contact with the liquid contents of the cell; however, a disadvantage of this technique is that it requires the use of toxic imaging agents.
PM Senior Scientist and Techna Core Lead Dr. Gang Zheng has developed a new non-toxic imaging agent that significantly enhances the quality of images generated using NOLM. The imaging agent is a nanoparticle that contains naturally derived compounds known as porphyrins, which form clusters within the nanoparticle. Use of this agent significantly enhances the intensity and contrast of NOLM live cell images. When the agent enters the cell, the porphyrin clusters degrade and become readily observable using a different type of fluorescence imaging.
Dr. Zheng explains, “These clusters are robustly produced, safe and easily incorporated into small vesicles, which makes them ideal for numerous biomedical applications such as drug delivery. The fact that they can be easily tracked inside the cell is particularly advantageous as it gives us an opportunity to examine how the nanoparticles degrade and how their presence influences cell function.”
This work was supported by the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research, the Terry Fox Research Institute, the National Science Foundation of China, the Canada Foundation for Innovation, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research and The Princess Margaret Cancer Foundation.
Organized aggregation of porphyrins in lipid bilayer for third harmonic generation microscopy. Cui L, Tokarz D, Cisek R, Ng KK, Wang F, Chen J, Barzda V, Zheng G. Angewandte Chemie International Edition. 2015 Sep 29. [Pubmed abstract]