Nanoparticle hardness controls the internalization pathway for drug delivery.

Area of Science:

• Biomedical Engineering
• Materials Science
• Computational Biology

Background:

• Nanoparticle (NP)-based drug delivery systems offer advantages like longer circulation and targeted release.
• Inefficient nanocarrier internalization is a key factor in drug resistance.
• Understanding NP-cell interactions is crucial for effective drug delivery.

Purpose of the Study:

• To investigate the effect of nanoparticle hardness on cellular internalization efficiency.
• To model different nanoparticle platforms (polymeric, liposome, solid) with varying hardness.
• To elucidate the mechanisms of NP internalization based on material properties.

Main Methods:

• Dissipative particle dynamics (DPD) simulations were employed.
• Three simplified NP models representing increasing hardness were designed.
• Cellular internalization pathways were analyzed based on NP properties.

Main Results:

• Nanoparticle hardness dictates the cellular entry pathway.
• Rigid NPs are internalized via endocytosis.
• Soft NPs exhibit frustrated endocytosis and utilize membrane penetration pathways due to shape deformation and ligand distribution.

Conclusions:

• Nanoparticle hardness is a critical parameter controlling internalization efficiency and pathway.
• Soft NPs may overcome endocytosis limitations through membrane penetration.
• The interaction between nanocarriers and drug molecules is vital for effective drug delivery.