Marshall G. G. Macduff

Understanding nanoparticle interactions with cells is fundamental to designing them for medical applications. Nanoparticles must interface with the cell surface to be bound and taken up. The glycocalyx is a carbohydrate layer coating the cell surface, rendering it negatively charged. Many researchers have noted that the glycocalyx affects nanoparticle uptake, but the mechanism remains unknown, Here, we investigate the interaction between the glycocalyx and nanoparticles at the cell surface in different cell types. The glycocalyx reduced the interactions between the nanoparticles and cells, thereby reducing cellular access, binding, and uptake. The magnitude of the effect is dependent on the nanoparticle charge. Fine-tuning the charge of nanoparticles can enhance the specificity of nanoparticle targeting. Understanding the role of the glycocalyx in nano-bio interactions will allow researchers to control the interactions of nanoparticles with the cell surface.

DNA barcoding is a common method for identifying the biodistribution of nanoparticles. DNA barcodes are typically encapsulated within nanoparticles to ensure accurate measurements by next-generation sequencing. This method limits the types of nanoparticles that can be screened. DNA can also be coated on nanoparticle surfaces. However, it is unclear whether surface-coated DNA can be used as barcodes because they can degrade, making the identification and quantification of nanoparticle designs challenging. Here, we developed strategies to reduce DNA degradation on nanoparticle surfaces, allowing surface-based DNA barcodes for biodistribution applications. We demonstrate that nanoparticle size, DNA density, and polymer length and density are essential design parameters for accurately identifying and quantifying nanoparticles in vivo. We found that chemical modification of DNA and shielding using neutral polymers reduce DNA degradation. We validated that surface barcoding can determine the in vivo distribution of nanoparticles. Our findings pave the way for the use of surface-based DNA barcodes for in vivo screening of nanoparticle formulations for targeted applications.