Elucidating the mechanism of cellular uptake and removal of protein

If the nanoparticles are already aggregated or agglomerated prior to binding to the membrane, their endocytosis patterns would differ from the endocytosis patterns of individual nanoparticles.

The degree of aggregation or agglomeration of the nanoparticles can be determined by measuring time-dependent change of size and surface charge of the nanoparticles in the culture medium.

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Because the formation of nanoparticle–protein complexes is mainly determined by surface chemistries of the nanoparticles, it is important to investigate which surface chemistry is the most favorable to form the nanoparticle–protein complex.Therefore, natural nanoparticle–protein complexes formed in biological environments would allow us to study how individual nanoparticles interact with various types of cells.In particular, exocytosis is of significance in the removal of nanoparticles with drugs and contrast agents from the body, while endocytosis is of great importance for the targeting of nanoparticles in disease sites.Here, we review the recent research on the endocytosis and exocytosis of functionalized nanoparticles based on various sizes, shapes, and surface chemistries.The stability lifetimes of the nanoparticle–protein complexes range from hours to days in the biological solutions.

The proteins covering the nanoparticle surface further prevent the individual nanoparticles from aggregation or agglomeration.Nanoparticles exposed to the bloodstream interact with opsonin proteins.When opsonin proteins attach to the surface of nanoparticles, they allow macrophages of the mononuclear phagocytic system (MPS) to easily recognize the nanoparticles and hence the nanoparticles eventually accumulate in the MPS organs, such as liver and spleen.Because drug delivery nanosystems transport pharmaceutical compounds in the body, it is important to understand their physiochemical properties to safely achieve a desired therapeutic effect.However, these drug delivery nanosystems have shown some limitations regarding the toxicity of the nanoscale materials in the body.4,5 In order to reduce their toxicity, it is crucial to study endocytosis, exocytosis, and clearance mechanisms for nanoparticles released from the nanoparticle–drug conjugates.The (hydrodynamic) size has been mainly analyzed using transmission electron microscopy (TEM) and dynamic light scattering (DLS) while the surface charge is determined by zeta potential measurements.