| Summary: | We here discuss shortly some pitfalls and challenges when investigating which endocytic mechanisms that are involved in cellular uptake of nanoparticles. We specifically discuss some common misunderstandings regarding studies claimed to demonstrate uptake via caveolae. Scientists in the nanomedicine field should be aware of that reduction in the membrane content of cholesterol by adding methyl-β-cyclodextrin not only removes caveolae, but inhibits other uptake mechanisms, such as macropinocytosis, as well. Furthermore, the general tyrosine kinase inhibitor genistein is not a specific inhibitor of uptake from caveolae. Moreover, one can still see that scientists in the field write that they want to direct transport of their particles to caveolae and caveosomes to avoid lysosomal degradation. However, caveosomes are artefacts caused by overexpression of caveolin-1 constructs, and ligands or particles taken up by caveolae are transported to endosomes and lysosomes as reported for other types of endocytosis.
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