Nanoparticles (NPs) show promising applications in biomedicine, catalysis, and energy harvesting. This applicability relies on controlling the material’s features at the nanometer scale. Surfactants, a unique class of surface-active molecules, have a remarkable ability to tune NPs activity; provide specific functions, avoid their aggregation, and create stable colloidal solutions. Surfactants also control nanoparticles’ nucleation and growth processes by modifying nuclei solubility and surface energy. While nucleation seems independent from the surfactant, NP’s growth depends on it. NP`s size is influenced by the type of functional group (C, O, S or N), length of its C chain and NP to surfactant ratio. In this paper, gold nanoparticles (Au NPs) are taken as model systems to study how nucleation and growth processes are affected by the choice of surfactants by Dissipative Particle Dynamics (DPD) simulations. DPD has been mainly used for studying biochemical structures, like lipid bilayer models. However, the study of solid NPs, and their conjugates, needs the introduction of a new metallic component. To represent the collective phenomena of these large systems, their degrees of freedom are reduced by Coarse-Grained (CG) models. DPD behaved as a powerful tool for studying complex systems and shedding some light on some experimental observations, otherwise difficult to explain.

HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV.