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A mechanistic understanding of the different uptake mechanisms in the cellular internalization of non-viral nucleic acid containing nanoparticles should open up possibilities to correlate uptake to intracellular processing and subsequently to transfection efficiency. One method to quantitatively assess contributions of different endocytic pathways is to inhibit them through the application of endocytic inhibitors. However, one should take extra care when using these chemicals as their cytotoxicity, effectivity and specificity is clearly cell dependent and not always as stated in literature. Therefore, these inhibitors should only be used after doing the appropriate control experiments and preferably in combination with complementary inhibition methods.