Porous-Medium Effect of Soft Protein Corona on the Photothermal Performance of Gold Nanoparticles in an Absorptive Blood Environment

Abstract The dynamically formed protein corona (PC) on gold nanoparticles (AuNPs) critically reshapes their photothermal performance in physiological environments. However, current theoretical models overwhelmingly simplify the entire PC as a homogeneous dielectric shell, neglecting the structurally distinct hard protein corona (HPC) and soft protein corona (SPC), particularly the intrinsically porous and loosely packed architecture of the SPC. Here, we introduce a porous-medium framework that integrates a fuzzy-shell model with the Maxwell-Garnett effective medium theory to quantitatively describe the gradient porosity distribution within the SPC. Crucially, we systematically compare the optical and thermal responses of this multilayered Au@HPC@SPC system in both an optically absorptive blood environment and idealized water, to approximate physiological conditions using an effective homogeneous absorptive blood model, while isolating the role of the complex biological fluid. Using finite-element simulations, we reveal an intriguing non-monotonic optical response most prominent in blood: during the initial growth of a hydrated, ultrathin SPC, the refractive index matching between the SPC and the surrounding medium suppresses the localized surface plasmon resonance (LSPR) redshift and reduces the extinction cross-section below that of bare AuNPs. This counterintuitive behavior, most pronounced in scattering-dominated larger particles, challenges the prevailing linear paradigm of corona-induced optical shifts. Building on this mechanistic insight, we establish a dual-parameter (LSPR shift and extinction ratio) orthogonal mapping that provides a theoretical retrieval framework for the in situ, non-destructive decoupling of hard and soft corona thicknesses. Furthermore, thermal analysis demonstrates that the entire protein corona (HPC and SPC) acts as a nanoscale thermal insulation layer, substantially enhancing local heating compared to homogeneous models. This work provides a quantitative basis for predicting nanoparticle photothermal performance in an effective homogeneous absorptive blood model and offers a novel optical strategy that, pending future experimental validation, could be used for characterizing the nanoparticle–biological interface.