Mononuclear phagocyte system nanoparticles

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In spite of all the advantages, cationic nanoparticles have some challenges. Some major drawbacks of these systems include instability, risk of aggregation, toxicity, opsonization and clearance by the mononuclear phagocyte system (MPS). To overcome these problems, cationic nanoparticles should be as small and neutral as possible and nanoparticles can be coated with PEG. PEG can provide a hydrophilic surface to nanocarriers and also a cationic surface charge and prevent opsonization. In this way, PEG-coated nanoparticles have a prolonged circulation life and protect photolytic degradation. 

Incubation of nanoparticles with cells in media leads to adsorption of serum proteins on their surface that increases the entry of nanoparticles into the cells by receptor-mediated endocytosis. However, during in vivo applications, designed nanoparticles can facilitate clearance by the reticuloendothelial system (mononuclear phagocyte system) because of serum proteins on the nanoparticle surface. Macrophages located in the liver and spleen remove nanoparticles bound with serum proteins (fibronectin, laminin, etc.). Binding of plasma protein is the first step for RES to remove the circulating nanosized drug carrier systems within a few hours. 

Iron oxide nanoparticles are usually taken up by macrophages in the mononuclear phagocytic system of the liver, spleen, lymphatics, and bone marrow.The associated blood half-lives depend on particle size and coating smaller nanoparticles have generally longer half-lives and are taken up by lymph nodes, whereas the bigger ones have shorter half-lives and are taken up by the liver and spleen. Particles penetrate the cell in large quantities and are subsequently transferred from early to deep endosomes. 

As stated previously, pSi particles are targets for internalization by cells of the mononuclear phagocyte system, and stealthing with PEG delays their uptake. For third-generation delivery systems, the first level of targeting for intravascularly administered particulates is the vascular endothehum. In vitro, vascular endothelial cells are able to internalize micron-sized pSi particles by phagocytosis and macropinocytosis (R.E. Serda et al, unpublished results). This is more compHcated in vivo, where serum opsonization coats the microparticles and alters their ability to adhere to the vascular wall. In this section we describe cellular uptake of pSi nanoparticles and microparticles, and examine the characteristics of pSi microparticles which alter this phenomenon. 

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