Biophysically inspired model for functionalized nanocarrier adhesion to cell surface: roles of protein expression and mechanical factors

摘要: In order to achieve selective targeting of affinity-ligand coated nanoparticles the target tissue, it is essential understand key mechanisms that govern their capture by cell. Next-generation pharmacokinetic (PK) models systematically account for proteomic and mechanical factors can accelerate design, validation translation targeted nanocarriers (NCs) in clinic. Towards this objective, we have developed a computational model delineate roles played protein expression cell membrane determining avidity functionalized NCs live cells. Model results show quantitative agreement with vivo experiments when specific non-specific contributions NC binding are taken into account. The accounted through extensive simulations multivalent receptor-ligand interactions, mechanics entropic such as undulations receptor translation. computed strongly dependent on ligand density, expression, bending membrane, well associated motion. Our predict levels intracellular adhesion molecule-1 (ICAM1)-coated lung, heart, kidney, liver spleen mouse, due endothelial for. effect other cells (such monocytes, etc.) do not improve predictions at steady state. We demonstrate predictive utility our predicting partitioning coefficients mice human tissues report statistical accuracy under different scenarios.