Enhanced hemocompatibility and cytocompatibility of halloysite nanotubes via the formation of a protein corona.

Halloysite clay nanotubes (HNTs) show promising applications as hemostatic materials and tissue-repairing materials owing to their unique tubular structure and physicochemical properties. When HNTs enter the body, the protein corona formed on HNTs affects the properties and behavior of the nanoparticles. Here, bovine plasma protein was used as a model protein to study the protein corona on HNTs (PC@HNTs), using chitosan-coated HNTs as a control. The formation of a stable protein corona layer on HNTs was confirmed by particle size, surface potential, and morphology, while circular dichroism analysis revealed significant changes in the protein secondary structure. PC@HNTs markedly improved hemocompatibility while retaining appreciable coagulation activity; for example, PC@HNTs-20% exhibited a hemolysis ratio below 1% at 1.5 mg mL-1. The protein corona on HNTs also reduced red blood cell deformation, phosphatidylserine externalization, reactive oxygen species generation, Ca2+ influx, K+ loss, and hemoglobin release. In RAW264.7 cells, PC@HNTs-20% reduced cellular uptake and oxidative stress while maintaining the cell viability above 85% at 800 μg mL-1. All these results demonstrated that the protein corona acts as a protective bio-interface that shields the reactive mineral surfaces, which weakens direct cell-material interactions and prevents harm to the cells. This work suggests that protein corona engineering can improve the biosafety of natural HNTs in vivo while preserving their hemostatic function, which provides evidence for the rational design of safe blood-contacting clay materials.