Glyco-nanotechnology: Sweet kisses of life and death

Advances in nanotechnology have played a fundamental role in revolutionizing biomedical sciences. It has delivered powerful tools with advanced diagnostic, therapeutical and analytical capabilities desirable for the fight against different human diseases. In particular, metal nanomaterials like quantum dots and gold have been widely used to obtain new knowledge about diseases, assay disease makers and facilitate therapeutic intervention owing to their outstanding magnetic electronic and optical properties.

Recently, glyco-nanotechnology, which combines the above unique nano-range properties with glycoscience, has attracted significant research attention. Glycans decorate almost all cell membrane proteins and sometimes lipids in the extracellular matrix. As a result, they govern intra- and inter-cellular communication and cell-microbe interactions via a triad of ligand bindings, recognition and cellular signaling. Thus, the disruption of the triads breaks the communication and information flow leading to rogue signaling and potential development of various pathogens.

Glyco-nanoparticles (GNPs) targeting aberrant extracellular matrix of the diseased tissue perform diagnostics by detecting and analyzing the changes in the magnetic, optical and electronic properties. GNPs are also engineered to detect disease biomarkers, correct aberrant signaling in the diseased tissues and provide therapeutic modalities. These desirable GNP capabilities are attributed to their ability to trigger signal transduction, molecular interactions and displaying multiple ligands to proteins and other cell glycans. The chemical and physical properties of GNPs have been modulated to develop potent analytical tools to aid the diagnosis of cancer biomarkers. Additionally, GNPs are promising glyco-vaccines as they elicit immune responses against tumor-associated antigens.

Nevertheless, despite the remarkable progress, glyco-nanotechnology is still an interesting field under intense research to uncover more powerful and robust techniques for fighting human diseases. Herein, Dr. Macy Payne and Professor Stefan Bossmann from The University of Kansas Medical Center-Cancer Biology together with Dr. Mausam Kalita from the University of California San Francisco provided critical expert opinion of the current status of glyco-nanotechnology research and development. Their review focused on the diagnosis, therapeutics and analysis of human diseases, especially cancer, neurological disorders and infectious diseases. The research team advocated nanomaterials with good performance for carbohydrate-based biosensing, bioimaging, vaccine preparation, and tumor targeted therapy, thereby becoming a robust tool in analytical chemistry and biomedical research. Their paper is currently published in the journal, Nanomedicine: Nanotechnology, Biology and Medicine.

The authors reported the critical role of glyco-nanotechnology in facilitating and promoting advanced biomarker sensing and detection, precise measurement of the protein-glycan interactions and improving quality control and analysis. The therapeutic potential of GNPs was discussed. For example, gold-lactose can disrupt the glycosynapse between endothelial and cancer cells, tetra-14 and tri-19F decorated gold induces immunological response against Staphylococcus pneumoniae while gold mannoside outcompetes HIV-1 viruses. Besides, GNPs are robust and powerful analytical tools. The lateral flow detection system based on paper and consisting of conjugated sialic acid and gold nanoparticles can detect the SARS-COV-1 spike glycoprotein in a very short time – a solution to Covid-19 testing problems.

Combining glycol-nanotechnology tools along with unique fluorescent characteristic of nanoparticles such as quantum dots and specificity of carbohydrate functionality enables real-time imaging studies, introduces new opportunities for several biomedical applications. More theranostic applications could also be developed by selecting and engineering specific tumour carbohydrate functionality along with unique featured fluorescent nanoparticles.

Other than pathology identification and remedy rogue signal transduction, GNPs have been engineered to map atherosclerosis and rapidly detect life-threatening contaminants in pharmaceutical-grade heparin. Glyco-nanotechnology is a promising technology for advancing diagnostic methods for improved detection of disease biomarkers using fluorescence imaging and magnetic resonance imaging as well as enhancing different therapeutics such as pneumonia vaccines and anti-adhesive cancer treatment.

In a nutshell, the authors reviewed the latest advances and development in glyco-nanotechnology from biomedical perspective, discussing the key features and a comprehensive understanding of this emerging technological field through multiple examples. The future potential and the range of applications of glyconanoparticles and the related carbohydrate-functionalized nanoparticles is ever-expanding, with applications across to target, image and treat infectious diseases and cancer. The field continues to progress at pace and impactful developments in the coming decade are anticipated. Professor Stefan Bossmann, the corresponding author told Medicine Innovates, “Whereas the majority of researchers concentrate on the interaction between small molecules and proteins, the majority of biological processes are governed by oligo- and polysaccharides at the surfaces of these proteins. Studying their interactions among each other and with other biological targets is mandatory to understand the biochemistry within a cell“