Computational Study of Ultra-Small Gold Nanoparticles with Amphiphilic Polymer Coating

Nanomedicine is rapidly evolving, with tailored nanoparticles enabling precise cellular-level interventions. Despite significant advances, challenges, such as rapid clearance and off-target effects, hinder the clinical translation of many nanosystems. Among the available nanoplatforms, gold nanoparticles (AuNPs) stand out due to their unique surface chemistry, low toxicity, and excellent biocompatibility. In this work, we present a multi-level computational investigation of ultra-small AuNPs coated with non-conventional amphiphilic polymer chains via atomistic and coarse-grained molecular dynamics. Through high-level-resolution atomistic simulations, we investigate how variations in grafting density impact the collective behaviors of these amphiphilic polymer chains within the coating by quantifying relevant conformational, structural, and energetic descriptors, such as the radius of gyration, terminal group presentation, polymer coating thickness, brush height, and solvation energy. Our results reveal a conformational shift of polymer chains from coiled to stretched as grafting density increases, with a direct effect on the polymer conformational regime, terminal group presentation, and coating thickness. In parallel, we further benchmark low-level coarse-grained models using the atomistic data as a reference, demonstrating their ability to correctly reproduce the atomistic trends. This computational investigation reveals how key descriptors vary with grafting density and provides the tools for conducting similar studies on broader time and length scales, thereby advancing the rational design of nanosystems for nanomedicine.