Assembling Biocompatible Polymers on Gold Nanoparticles: Toward a Rational Design of Particle Shape by Molecular Dynamics

[Image: see text] Gold nanoparticles (AuNPs) have received great attention in a number of fields ranging from the energy sector to biomedical applications. As far as the latter is concerned, due to rapid renal clearance and a short lifetime in blood, AuNPs are often encapsulated in a poly(lactic-co-glycolic acid) (PLGA) matrix owing to its biocompatibility and biodegradability. A better understanding of the PLGA polymers on the AuNP surface is crucial to improve and optimize the above encapsulation process. In this study, we combine a number of computational approaches to explore the adsorption mechanisms of PLGA oligomers on a Au crystalline NP and to rationalize the PLGA coating process toward a more efficient design of the NP shape. Atomistic simulations supported by a recently developed unsupervised machine learning scheme show the temporal evolution and behavior of PLGA clusterization by tuning the oligomer concentration in aqueous solutions. Then, a detailed surface coverage analysis coupled with free energy landscape calculations sheds light on the anisotropic nature of PLGA adsorption onto the AuNP. Our results prove that the NP shape and topology may address and privilege specific sites of adsorption, such as the Au {1 1 1} crystal planes in selected NP samples. The modeling-based investigation suggested in this article offers a solid platform to guide the design of coated NPs.