Most biomedical applications involving nanoparticles require targeted delivery into specific cells. To develop more potent nanocarriers, it is important to understand their cellular uptake mechanisms.
While traditional small molecule drugs enter cells mainly through passive diffusion or active transport, nanomedicines are transported across the membrane via endocytosis. Endocytosis is generally classified into phagocytosis, pinocytosis and receptor-mediated endocytosis. Of the three primary endocytosis mechanisms, pinocytosis is mainly a passive mechanism of moving small liquid molecules inside the cell membrane and is not largely applicable to our nanoparticles. Most nanoparticles above ~5 nm in size are internalized into cells by either receptor-mediated endocytosis or phagocytosis.
Phagocytosis or ‘cell eating’ is the non-specific internalization of particulates. Immune cells including macrophages, neutrophils and monocytes as well as cancer cells are also known to internalize nanoparticles through phagocytosis. Relatively larger particles are more likely to use this route. But the cargo contained in the phagosomes will be destroyed by acidification and enzymolysis in the lysosomes. Therefore, to produce desired effects, nanomedicines need to bypass this route to avoid degradation.
If nanoparticles are coated with biomolecules (e.g. peptides, proteins, antibodies, ligands, affibodies, aptamers) specific to receptors on the surface of cells, the nanoparticles will bind to the outer membrane of the cell. If those receptors naturally induce receptor-mediated endocytosis, nanoparticles will follow and be sequestered inside the cell. Therefore, if you use targeted nanoparticles (nanoparticles conjugated with cell-specific biomolecules) then the dominant form of cellular uptake, by design, is receptor-mediated endocytosis.
In some cases (such as macrophages or certain cancer cell lines) phagocytosis may be adequate for cellular uptake of nanoparticles. However, in most cases receptor mediated endocytosis is preferred over phagocytosis.
Depending on the size and surface charge and a few other factors, a specific cellular internalization route may be preferred over others. The following factors are believed to contribute to the entry of nanoparticles into cells and influence their final destination:
Despite the growing body of literature in this area, controlling the intracellular delivery fate and localization of nanoparticles remains a major challenge. Feel free to contact us if you need additional information on the uptake of a specific category of nanoparticles.
In addition to gold nanoparticles, NanoHybrids also develops nanocarriers that are custom designed for intracellular delivery and endosomal escape of therapeutic agents.
If you are considering using nanoparticles for targeted drug delivery, drop us a line and we can help with particle design & formulation.
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