Gold nanoparticles (AuNPs) are promising materials for many bioapplications. However, upon contacting with biological media, AuNPs undergo changes. The interaction with proteins results in the so‐called protein corona (PC) around AuNPs, leading to the new bioidentity and optical properties. Understanding the mechanisms of PC formation and its functions can help us to utilise its benefits and avoid its drawbacks. To date, most of the previous works aimed to understand the mechanisms governing PC formation and focused on the spherical nanoparticles, although non‐spherical nanoparticles are designed for a wide range of applications in biosensing. In this work, we investigated the differences in PC formation on spherical and anisotropic AuNPs (nanostars in particular) from the joint experimental (extinction spectroscopy, zeta potential and surface‐enhanced Raman scattering [SERS]) and computational methods (the finite element method and molecular dynamics [MD] simulations). We discovered that protein does not fully cover the surface of anisotropic nanoparticles, leaving SERS hot‐spots at the tips and high curvature edges ‘available’ for analyte binding (no SERS signal after pre‐incubation with protein) while providing protein‐induced stabilization (indicated by extinction spectroscopy) of the AuNPs by providing a protein layer around the particle's core. The findings are confirmed from our MD simulations, the adsorption energy significantly decreases with the increased radius of curvature, so that tips (adsorption energy: 2762.334 kJ/mol) would be the least preferential binding site compared to core (adsorption energy: 11819.263 kJ/mol). These observations will help the development of new nanostructures with improved sensing and targeting ability.

Coronary artery calcification (CAC) is associated with major adverse cardiovascular events.^{1 – 3} To date, the clinical impact of arterial calcification on local plaque vulnerability remains unclear,⁴ but the extent of CAC is associated with worse outcomes in the general population and in patients undergoing revascularization.^5,6 In addition, the presence of calcifications leads to under-expansion during percutaneous coronary intervention (PCI).⁷ The previous study demonstrated that severely calcified plaques undergoing PCI were associated with higher procedural complications and lower success rates.⁸ Hence, detection of calcified region is important for PCI treatment. For example, in the heavily calcified lesions, it is hard to cross or dilate a coronary stenosis with PCI devices such as balloons or stents.⁹ However, rotational atherectomy facilitates delivery or expansion for the treatment of complex calcified lesions. Furthermore, other available treatment strategies such as cutting and scoring balloons improve vessel compliance by creating discrete incisions instead of producing small particles to ablate the heavily calcified plaque for rotablation.⁴ For above reasons, a cardiologist pays more attention to the calcified lesion when making a clinical decision. Therefore, accurate identification and quantification of calcified lesion is crucial when treating patients with advanced coronary atherosclerosis.