In Vitro and In-Silico Assessment of Gaussian Curvature-driven Internalization Kinetics of Nanoparticles

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Nanoparticle (NP) cellular uptake is crucial for biomedical applications but remains inefficient.
• Low uptake necessitates higher doses, increasing toxicity risks.

Purpose of the Study:

• To investigate the effect of nanoparticle Gaussian curvature on cellular uptake efficiency.
• To demonstrate that negative Gaussian curvature enhances NP internalization.

Main Methods:

• Synthesis of gold nanorods (GNR) and gold nanodogbones (GDB) with varying Gaussian curvatures.
• Quantification of cellular uptake using ICP-OES analysis in A549 and NIH3T3 cells.
• Confocal microscopy and molecular simulations to validate uptake mechanisms.

Main Results:

• Gold nanodogbones with negative Gaussian curvature (GDB6) showed significantly higher uptake than GNR.
• GDB6 uptake was 140% higher in A549 cells and 77% higher in NIH3T3 cells compared to GNR.
• Molecular simulations confirmed that negative curvature lowers the energy barrier for membrane translocation.

Conclusions:

• Nanoparticle Gaussian curvature is a critical factor for enhancing cellular uptake.
• Negative Gaussian curvature facilitates efficient NP internalization by reducing membrane bending energy.
• This finding offers valuable insights for designing advanced nanomaterials for drug delivery and other biomedical uses.