Solid lipid nanoparticles release DNA upon endosomal acidification in human embryonic kidney cells

Nanotechnology can produce materials with unique features compared to their bulk counterparts, which can be useful for medical applications (i.e. nanomedicine). Among the therapeutic agents used in nanomedicine, small molecules or biomacromolecules, such as proteins or genetic materials, can be designed for disease diagnostics and treatment. To transport these biomacromolecules to the target cells, nanomedicine requires nanocarriers. Solid lipid nanoparticles (SLNs) are among the promising nanocarriers available, because they can be made from biocompatible materials and present high stability (over one year). In addition, upon the binding genetic material, SLNs form SLNplexes. However, little is yet known about how cells process these SLNplexes-in particular, how internalization and endosome acidification affects the transfection mediated by SLNplexes. Therefore, we aim to investigate how these processes affect SLNplex transfection in HEK293T cells. We find that the SLNplex is mainly internalized by clathrin-mediated endocytosis, which is a fast and reliable pathway to transfection, leading to approximately 60% transfection efficiency. Interestingly, upon acidification (below pH 5.0), the SLN seems to release its DNA content, which can be an essential step for SLNplex transfection. The underlying mechanisms described in this work may help improve SLNplex formulations and transfection efficiency. Moreover, these advances can improve the field of nanomedical research and bring new ways to cure diseases.