Computation Simulation of Nanoparticle Endocytosis: Do Individual Particles Synergize with Each Other for Cell Entry?

After decades of research, nanomaterials have been widely used in various applications, including biomedical materials as therapies themselves or drug carriers. In such cases, cell entry is a crucial step, which has been extensively studied. However, one fundamental and yet long-overlooked question is whether there is any synergy among individual nanoparticles (NPs) in this process. We previously reported the bystander uptake of NPs, a synergistic phenomenon in which NPs facilitate each other for cell entry. Moreover, we then harnessed molecular dynamics simulation, a method that has been used to study NP-cell interactions, to elicit the biophysical basis of bystander uptake. This review provides a brief overview of current nanotechnology for intracellular delivery, the underlying endocytic pathway, and the use of molecular dynamics simulation on NP-cell interaction. Our emphasis is then on the bystander uptake system and its translational applications and the recent advance in understanding its mechanism with computational simulation and biophysics. These efforts may provide novel insights on the synergy among individual NPs during cell encounter and endocytosis and open new avenues to understand NP uptake with computation simulation and biophysical perspective.