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

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cell Biology

Background:

• Nanotechnology enables the creation of novel materials for medical applications, known as nanomedicine.
• Solid lipid nanoparticles (SLNs) are biocompatible and stable nanocarriers used to deliver therapeutic agents like genetic material.
• SLNs complexed with genetic material are termed SLNplexes, but their cellular processing and transfection mechanisms remain unclear.

Purpose of the Study:

• To investigate the cellular uptake mechanisms of SLNplexes in HEK293T cells.
• To determine the effect of endosome acidification on SLNplex-mediated gene transfection.
• To elucidate the pathways involved in SLNplex processing for improved nanomedicine applications.

Main Methods:

• Utilized HEK293T cells to study SLNplex-cell interactions.
• Investigated cellular internalization pathways, focusing on clathrin-mediated endocytosis.
• Analyzed the impact of endosomal pH changes on DNA release from SLNplexes.

Main Results:

• SLNplexes are primarily internalized through clathrin-mediated endocytosis, a highly efficient cellular uptake pathway.
• Transfection efficiency reached approximately 60% via this mechanism.
• Acidification of endosomes below pH 5.0 triggers the release of DNA content from the SLNplex, a critical step for transfection.

Conclusions:

• Clathrin-mediated endocytosis is a key pathway for SLNplex cellular delivery and transfection.
• Endosomal acidification is essential for releasing genetic material, facilitating successful transfection.
• Understanding these mechanisms can optimize SLNplex formulations for enhanced gene delivery in nanomedicine.