To measure cellular uptake of nanoparticles, flow cytometry is a commonly used method that quantifies nanoparticle presence within cells by analyzing fluorescence intensity. To enhance the uptake of non-targeted nanoparticles, strategies such as modifying their surface properties, coating them with proteins to create a "corona," or adjusting their size and charge can be effective. If fluorescent nanoparticles are not entering cells, it may be due to their size or surface characteristics. Improving their uptake can involve using smaller nanoparticles, altering their surface chemistry, or employing techniques like electroporation or microinjection to facilitate entry into cells.

Measure the zeta potential of the cells and, separately, the nanoparticles. If they both carry the same sign charge, it will hinder uptake. This is why lipid nanoparticles used for mRNA delivery (COVID vaccines) are cationic.