Nanoparticles can be used as powerful tools to administer vaccines and prevent serious diseases, such as in the treatment of COVID-19 and to deliver chemotherapy drugs to cancer cells to eradicate cancer cells and leave healthy cells unharmed. For cancer patients, this has the potential to reduce the severe side effects that result from the toxicity of chemotherapy drugs. Unfortunately, no clinically applied selective nanoparticle treatment (also known as nanotherapeutics) yet exists, and research is focused on improving and understanding current nanotherapeutics. For her PhD research, Laura Woythe took a closer look at nanoparticles and cancer cells to design selective nanotherapeutics using advanced optical microscopy techniques.

To improve the nanoparticles’ ability to target cancer cells, scientists can use how the nanoparticles interact with specific cellular biomarkers, or “receptors,” on the surface of the cells. For this purpose, molecules or “ligands” that recognize specific cellular receptors are placed on the surface of the nanoparticles.

However, this so-called functionalization process is difficult to control due to the small size of the nanoparticles, which causes some molecules to be misplaced, malfunction or be incorrectly attached to the nanoparticle surface. All of these reduce the ability of nanoparticles to interact with cancer cells in the intended way.

Furthermore, questions remain about the efficiency of such attachment protocols and whether the number of molecules we attach is efficient enough to target cancer cells. The challenges lie in the small size of the molecules and cellular receptors and the limited quantitative methods that are available to estimate the number of molecules on the nanoparticle surface. In other words, how can scientists count the number of molecules on the surface of nanoparticles to test whether nanoparticles can be effective against cancer cells?

Super-resolution microscopy

For her PhD research, Laura Woythe investigated the functionality of molecules attached to nanoparticles to selectively target cancer using advanced optical microscopy techniques or “super-resolution” optical microscopy.

Super-resolution microscopy encompasses a group of microscopic techniques that have a resolution that is 10 times higher than conventional optical microscopy. This allows visualization of nanometric structures, such as nanoparticles and cellular receptors, in the 10 to 100 nanometer (nm) range. This size range is equivalent to visualizing structures up to 5000 times smaller than a human hair.

Using super-resolution microscopyWoythe and her colleagues were able to rely on individual ligands nanoparticles and receptors on cancer cells, thereby allowing the fine-tuning of the targeting interaction. These numbers can go a long way toward developing more effective nanotherapeutic delivery.

Woythe’s research is an important step toward a better understanding of nanomaterials for biomedical applicationsin particular, selective cellular targeting of cancer cells and diseased cells without affecting healthy tissue, thus minimizing potential side effects and the burden it causes cancer patients.

Selective cancer nanoparticle targeting under the microscope

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