Zooming in on nanomedicine’s ‘crown’

Dr. Sara Sheibani, an affiliated academic member at Department of Anatomy and Cell Biology, and Dr. Kaustuv Basu, staff scientist at the Facility for Electron Microscopy Research, McGill University, are part of an international team of researchers that has developed a new method to better understand how nanomedicines — emerging diagnostics and therapies that are very small yet very intricate — interact with patients’ biomolecules.

With the emergence of nanotechnology decades ago and its application in nanomedicine, the use of nanoscale materials, such as biocompatible nanoparticles as drug delivery system, diagnosis, and therapeutic tools has contributed significantly to the advancement of biomedical research. However, despite substantial progress, laboratory and clinical research in nanomedicine currently face serious challenges in research and development, clinical trials, and successful commercialization processes.

One of the most promising aspects of nanomedicine has been its capability to offer site-specific targeted treatment. “Targeted, personalized medicine involving nanomaterials has the potential to revolutionize diagnosis, drug delivery, and therapeutics,” says Dr. Sheibani. “Most studies in nanomedicine, however, have overlooked several important factors including the alteration of functionalized nanoparticles (NPs) upon exposure to culture medium and body fluid.”

To address some of these challenges, Dr. Sheibani collaborated with Dr. Morteza Mahmoudi, Assistant Professor in the Department of Radiology and the Precision Health Program at Michigan State University, who is a world leader in designing and developing nanomaterials for diagnostic and therapeutic applications. In a recent joint study, the results for which were published online January 25 in the journal Nature Communications,  Dr. Sheibani and her colleagues at McGill used the most advanced state-of-the-art cryo-microscopy techniques, available only at the McGill Facility of Electron Microscopy Research in Canada, to investigate the morphological feature of proteins and biomolecules coating on the surface of NPs referred to as a corona (not to be confused with the novel coronavirus), the Latin word for crown. This corona contains clues about how nanoparticles interact with a patient’s biology. Now, the team has shown how to get an unprecedented view of that corona at atomic scale.

“One of the main challenges has been our poor understanding of the mechanism(s) of protein–protein interaction within the corona and the relationship and association of biomolecules with the surface of NPs,” notes Dr. Sheibani. The application of cryo-electron microscopy, cryo-electron tomography, 3D reconstruction and image processing, and image simulation showed the variation in the structure and distribution of the biomolecules in the coronas of hundreds of individual NPs. It also enables the visualization of the individual biomolecules.

“Our findings demonstrate that the application of therapeutic NPs is more challenging than predicted in the published literature,” adds Dr. Sheibani. “Biosystems, including the immune system, respond to NPs at the level of a single NP. The heterogeneous nature of the biomolecular corona (BC), therefore, significantly affects their safety and biological efficacy. The results of our study could lead to a better understanding of the function of the BC and its nonuniform behavior, at a resolution of a single NP, which significantly affects the outcomes of in vitro and in vivo experiments as well as most of the reported clinical trials. It helps the nanomedicine community to define the accuracy and reliability of proteomics and analytical chemistry data of the BC at the surface of NPs; the latter is important for defining the suitability of various types of NPs for clinical applications.”

Image: Fig: Representation of distribution pattern of clusters of biomolecules of the surface of individual NPs. The image is a snapshot generated from the 3D volume of the following movie.

February 25, 2021