Interaction of Cationic Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Human Melanoma Cells

Abstract

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.

Keywords::

• cathepsin
• cationic iron oxide NPs
• cell uptake
• electron microscopy
• human fibroblasts
• human melanoma
• lysosomes
• spheroids
• transferrin receptor

Financial & competing interests disclosure

This work was supported by grants from the Swiss National Scientific Research Foundation (grant No. 3152A0–105705), the Swiss League and Research against Cancer (grant No KLS-01308–02–2003) and the EC 7th Framework Program project No. 201335 “NanoTEST”. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank Jacques Dubochet for very helpful comments and analysis of the cryoelectron microscopy images, and Antonio Mucciolo, Michel Bonin, Auxia Montoro and Catherine Chapuis Bernasconi for excellent technical assistance.

The authors thank D Rimoldi (Ludwig Institute, Lausanne, Switzerland) for the kind gift of human Me300 melanoma cells. The authors also thank M Benathan, (Dermatology, CHUV, Switzerland) for the kind gift of human PG98/5 skin fibroblasts.

Additional information

Funding

This work was supported by grants from the Swiss National Scientific Research Foundation (grant No. 3152A0–105705), the Swiss League and Research against Cancer (grant No KLS-01308–02–2003) and the EC 7th Framework Program project No. 201335 “NanoTEST”. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.