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Interaction of Spin-Labeled HPMA-based Nanoparticles with Human Blood Plasma Proteins

We revised current understanding of the protein corona that is created on the surface of the nanoparticles in blood plasma after intravenous injection. These nanoparticles are based on N-(2-hydroxypropyl)methacrylamide (HPMA) and have been tested both in vitro and in vivo. We studied the interaction of nanoparticles with blood plasma and selected blood plasma proteins by electron paramagnetic resonance (EPR), isothermal titration calorimetry (ITC), dynamic light scattering (DLS), and cryo transmission electron microscopy (cryo-TEM). The copolymers were labeled with TEMPO radicals to monitor changes in polymer chain dynamics caused by protein adsorption. It was found that HSA, LDL, HDL, IgG and plasma have very low binding affinity to nanoparticles. In contrast with the “hard-soft coronas” paradigm used to describe a double shell layer of proteins, we observed no hard corona around HPMA-based nanoparticles. Our study suggests that a classical “hard corona-soft corona” paradigm is not valid for all types of nanoparticles but rather represents an extreme case for some types of charged and hydrophobic nanoparticles.

HPMA copolymers ; drug delivery ; blood plasma ; proteins ; EPR/ESR ; light scattering ; Cryo-TEM

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