Nanoparticles (NPs) exposed to a biological milieu will strongly interact with proteins, forming “coronas” on the surfaces of the NPs. The protein coronas (PCs) affect the properties of the NPs and provide a new biological identity to the particles in the biological environment. The characterization of NP-PC complexes has attracted enormous research attention, owing to the crucial effects of the properties of an NP-PC on its interactions with living systems, as well as the diverse applications of NP-PC complexes. The analysis of NP-PC complexes without a well-considered approach will inevitably lead to misunderstandings and inappropriate applications of NPs. This review introduces methods for the characterization of NP-PC complexes and investigates their recent applications in biomedicine. Furthermore, the review evaluates these characterization methods based on comprehensive critical views and provides future perspectives regarding the applications of NP-PC complexes.

The endoplasmic reticulum (ER) plays crucial roles in maintaining protein quality control and regulating dynamic Ca²⁺ storage in eukaryotic cells. However, the proteostasis system involved in ER-mediated protein quality control has not been fully characterized. Here we show that Ca²⁺ triggers the condensation of PDIA6, an ER-resident disulfide isomerase and molecular chaperone, into quality control granules. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the PDIA6 condensates recruit proinsulin, thereby accelerating the oxidative proinsulin folding and suppressing the proinsulin aggregation inside quality control granules, essential for secretion of insulin.