Subcellular compartment targeting of layered double hydroxide nanoparticles

Area of Science:

• Nanotechnology
• Materials Science
• Biomedical Engineering

Background:

• Layered double hydroxide (LDH) nanoparticles offer potential as non-viral drug delivery agents.
• Their properties include low cytotoxicity, biocompatibility, and controlled drug loading and release.
• Morphology control is key for targeted cellular delivery.

Purpose of the Study:

• To investigate the cellular uptake and subcellular localization of two distinct Mg(2)Al-LDH nanoparticle morphologies.
• To explore the mechanisms of cellular internalization and endosomal escape.
• To assess the potential for morphology-dependent targeted delivery to specific cellular compartments.

Main Methods:

• Preparation of Mg(2)Al-LDH nanoparticles labeled with fluorescein isothiocyanate (FITC) in hexagonal sheet and rod morphologies.
• Transfection of mammalian cell lines with LDH(FITC) nanoparticles.
• Microscopy to observe cellular uptake and localization.
• Inhibition experiments to elucidate the endocytosis pathway.
• Investigation of endosomal escape mechanisms.

Main Results:

• LDH(FITC) nanorods were rapidly translocated into the nucleus.
• LDH(FITC) nanosheets were retained in the cytoplasm.
• Cellular uptake was identified as a clathrin-mediated, time- and concentration-dependent endocytosis process.
• Endosomal escape is proposed to occur via nanoparticle deacidification.
• Nuclear targeting of nanorods likely involves active, microtubule-mediated transport.

Conclusions:

• Controlling LDH nanoparticle morphology enables targeted delivery to distinct subcellular compartments (nucleus or cytoplasm).
• This morphology-dependent targeting mechanism has significant potential for cellular biomedicine applications.
• Further research is needed to fully elucidate the nuclear targeting mechanism for nanorods.