Applications of nanoparticles in the bio-medical field like nano-medicine, molecular imaging probes, fluorescence marker, gene carriers, are developing quickly owing to the unique characteristics of nanoparticles. Among these applications, the interaction of nano-particles with the living cells is of critical importance. The complex chemical properties and biological activities of the particles bring about undesirable cytotoxic potentials and special cell internalization. According to previous studies, the cell uptake kinetics of nanoparticles mainly depend on the concentration difference between extracellular and intracellular nanoparticles, the surface electric charge of the nanoparticle, and the active transport of the cell. For example, Ginzburg’s thermodynamic simulation and Park’s three-dimensional phase-field model quantitatively explain the transitions in membrane morphology after exposure to nanoparticles with different surface charge, respectively. However, recent studies have shown that the gold nanoparticles coated with hydrophilic and hydrophobic functional groups with the same concentration but in different orders, completely exhibit quite different intrusion ability at 4°C when the active transport of the cell is greatly inhibited. The results suggest that the interaction energy of nanoparticles and cell membranes may be another driving force for the nanopartcles’ mass transfer across the cell membrane. Thus, in this paper, the interaction energy of the differently coated nanoparticles (P) with cell membrane (M) in water (W) is studied theoretically and results are used to explain the former experimental findings.

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