Journal
NANOMEDICINE
Volume 5, Issue 7, Pages 1075-1087Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.10.79
Keywords
cathepsin; cationic iron oxide NPs; cell uptake; electron microscopy; human fibroblasts; human melanoma; lysosomes; spheroids; transferrin receptor
Funding
- Swiss National Scientific Research Foundation [3152A0-105705]
- Swiss League and Research against Cancer [KLS-01308-02-2003]
- EC [201335]
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Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) are currently under development for the intracellular delivery of therapeutics. However, the mechanisms of cellular uptake and the cellular reaction to this uptake, independent of therapeutics, are not well defined. The interactions of biocompatible cationic aminoUSPIONs with human cells was studied in 2D and 3D cultures using biochemical and electron microscopy techniques. AminoUSPIONs were internalized by human melanoma cells in 2D and 3D cultures. Uptake was clathrin mediated and the particles localized in lysosomes, inducing activation of the lysosomal cathepsin D and decreasing the expression of the transferrin receptor in human melanoma cells and/or skin fibroblasts. AminoUSPIONs deeply invaded 3D spheroids of human melanoma cells. Thus, aminoUSPIONs can invade tumors and their uptake by human cells induces cell reaction.
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