Internalization of Lipid-Coated Gold Nanocomposites and Gold Nanoparticles by Mouse SC-1 Fibroblasts in Monolayer and Spheroids

In this study, we have established that unique composite particles (MLNCs) carried siRNA on a gold core and were covered with a lipid shell. MLNCs successfully delivered siRNa into cells in the presence of serum. We developed the photofixation method, allowing us to obtain MLNCs bearing a fixed protein corona. To understand the mechanisms of the influence that the protein corona has on the interaction of particles with cells, it is necessary to study the interaction of "naked" MLNCs with cells. This study aimed to examine the pathways of MLNC penetration into SC-1 fibroblasts used to confirm the efficacy of siRNA delivery. We studied fibroblasts in monolayer and spheroid form, and citrate AuNPs were used as a comparison particle. The same particles served as cores for MLNCs. The obtained results showed active penetration by clathrin-mediated endocytosis of "naked" MLNCs into SC-1 fibroblasts, regardless of the form of cultivation. AuNPs penetrated into monolayer fibroblasts by macropinocytosis and into spheroids by clathrin-mediated endocytosis. The penetration depth into the spheroids was about 40 μm for both types of particles (spheroid size was 350-400 μm). The particles migrated through the intercellular spaces, passing through intercellular contacts.