Abstract
The use of nanoparticles as carriers to deliver pharmacologically active compounds to specific parts of the body via the bloodstream is a promising therapeutic approach for the effective treatment of various diseases. To reach their target sites, nanocarriers (NCs) need to circulate in the bloodstream for prolonged periods without aggregation, degradation, or cargo loss. However, it is very difficult to identify and monitor small-sized NCs and their cargo in the dense and highly complex blood environment. Here, we present a new fluorescence correlation spectroscopy-based method that allows the precise characterization of fluorescently labeled NCs in samples of less than 50 μL of whole blood. The NC size, concentration, and loading efficiency can be measured to evaluate circulation times, stability, or premature drug release. We apply the new method to follow the fate of pH-degradable fluorescent cargo-loaded nanogels in the blood of live mice for periods of up to 72 h.
Highlights
The use of nanocarriers (NCs) to deliver small drug molecules, proteins, or nucleic acids is a highly promising therapeutic approach
Under aqueous buffer conditions that is after preparation of the NCs and during their shelf life these parameters can be monitored relatively using a number of experimental techniques including dynamic light scattering, nanoparticle tracking analysis, size exclusion chromatography, zeta potential, and transmission electron microscopy (TEM).[20,21]
NCs that stick to blood cells or are endocytosed by, for example, cells of the reticuloendothelial system can not be characterized directly, but through the decrease of their concentration in the liquid part of the blood, their disappearance during circulation can be concluded indirectly
Summary
The use of nanocarriers (NCs) to deliver small drug molecules, proteins, or nucleic acids is a highly promising therapeutic approach. Sufficient nanoparticle integrity and prolonged NC stability in the blood stream are key prerequisites for NCs if there is to be reliable therapeutic benefit.[22,23] The high concentration of cells, numerous proteins, and other components in the blood can strongly affect the NCs, for example, by the formation of a protein corona,[24,25] aggregation, decomposition, or premature release of the drug cargo. It is, crucial that we are able to track the fate of systemically administered NCs, especially during their circulation in the blood. Given the very small size of the usual NCs (between 10 and 100 nm), the high complexity of the blood components, and variant mechanical forces, this has to date remained a challenging task
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