Original ArticleTargeted uptake of folic acid-functionalized iron oxide nanoparticles by ovarian cancer cells in the presence but not in the absence of serum
Graphical Abstract
Targeted, i.e. receptor-mediated cellular uptake of folic acid (FA)-conjugated iron oxide nanoparticles is shown for particles with SiO2 coating, but not for particles with poly(ethylene glycol), PEG coating. Both particles displayed excellent biocompatibility.
Section snippets
Synthesis of folic acid-conjugated Fe3O4 nanoparticles
Fe3O4-PEG nanoparticles were synthesized following a slightly modified solvothermal process previously reported by Yan et al.20 Experimental details are provided in the Appendix. Core shell nanostructures were synthesized using a variation of the well-known Stöber process. The synthetic pathway for Fe3O4-SiO2-FA particles and Fe3O4-PEG-FA particles is shown schematically in Figure 1, A and B, and experimental details are provided in the Appendix. The Fe3O4-PEG-FA and Fe3O4-SiO2-FA nanoparticles
Synthesis of Fe3O4-PEG-FA and Fe3O4-SiO2-FA nanoparticles
Magnetic iron oxide nanoparticles were synthesized by solvothermal decomposition of iron salt in aqueous media. TEM analysis of Fe3O4-PEG particles showed spherical morphology with a narrow size distribution and an average primary particle size of 18.4 nm (Figure 2, A). The HR-TEM additionally proves the high crystallinity of the particles and the formation of the Fe3O4 phase (Figure 2, B). The phase structure was further confirmed by XRD analysis (Figure 2, C) and is corroborated by the
Discussion
In the present study, we evaluated the biocompatibility and specific targeting of FA-conjugated iron oxide nanoparticles with different intermediate surface coatings. Using a model of ovarian cancer cells with/without expression of FR-α, we have demonstrated specific cellular uptake of the SiO2-coated nanoparticles, while uptake of PEG-coated nanoparticles also occurred but this was not specific i.e. not mediated through a FR-α-dependent pathway. Notably, specific uptake was not seen in the
Acknowledgments
We thank Dr. Kjell Hultenby, Electron Microscopy Core Facility, Karolinska Institutet, for assistance with TEM imaging of cellular uptake of NPs. Ramy El-Sayed, Karolinska Institutet, is acknowledged for the HR-TEM shown in Figure 3, A. Margaretha Grandér and Brita Palm, Karolinska Institutet, are thanked for assistance with ICP-MS measurements.
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2022, Journal of Controlled ReleaseCitation Excerpt :Another example is the folate molecule which was discussed above in detail. One study showed that the internalization of folate-modified iron NPs by SKOV-3 cells was highly dependent on the presence of serum [138]. It is worth noting that this study was performed in the presence of FBS.
Author contributions: B.F. and S.M. conceived and designed the study; A.K., L.H., and N.F. performed and analyzed the biological experiments under the supervision of B.F.; L.W. and L.H. synthesized and characterized the nanoparticles, under the supervision of S.S. and S.M.; M.V. supervised the ICP-MS experiments; A.K. drafted the manuscript with B.F. and S.M.; all authors discussed the results and approved the final version of the manuscript.
Conflict of interest statement: None of the authors have any conflict to declare related to the study.
Sources of support: This work was supported by the Seventh Framework Programme of the European Commission (FP7-NANOMMUNE-Grant Agreement No. 214281), the Swedish Cancer and Allergy Foundation, and the University of Cologne, Cologne, Germany.
- 1
These authors contributed equally to this work.
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Present affiliation: King’s College London, Analytical and Environmental Sciences Division, London, United Kingdom.