Intracellular Nano-Fate / Tissular biodegradation of nanoparticles

With the growing medical use of magnetic nanoparticles, in particular for cell therapies, it is crucial to study their long-term intracellular fate within living tissues.

We provided multiscale quantitative methods to study intracellular iron oxide nanoparticle degradation, showing an unexpected near-total nanoparticle degradation during long-term maturation of a stem cell model tissue (Figure 1, Mazuel et al. ACS nano 2016)

In brief, we developed stem cell spheroids as new biological tools to monitor intracellular nanoparticle degradation, and we managed to perform single spheroid magnetism in situ as a fingerprint of nanoscale transformations. Remarkably, and unexpectedly, the nanoparticles were found to be more than 90% purged inside the tissue in the first ten days of tissue maturation, barely affecting cellular iron homeostasis. The same massive degradation was recapitulated at the single endosome level, using a unique approach based on single purified endosome nano-magnetophoresis.

These results evidencing for the first time a total breakdown of nanoparticles by endosomes in stem cells composing a model tissue bodes well for their safety in medical applications, especially regenerative medicine.

Figure 1 : Monitoring the intracellular biodegradation of iron oxide nanoparticles with magnetic methods, at both the tissue and single endosome levels. Mazuel et al. ACS nano 2016.

Figure 2 : Monitoring the intracellular fate of Iron Oxide Nanoflowers@Au showed different transformation scenarios, from the release of small gold seeds when the magnetic core is dissolved (interesting for long-term elimination) to the protection of the magnetic core (interesting for long-term therapeutic applicability).

Beyond its obvious nanosafety implications, the impact of the cellular environment on nanomaterials also raises concerns as to their therapeutic applicability, for either the tissue engineering field (long-term stimulation of engineered tissues), or for cancer therapies (serial treatments). It can thus be beneficial to protect iron oxide nanoparticles to massive intracellular dissolution.

We have showed (collaboration with Ali Abou-Hassan, PHENIX, UPMC) that a gold shell can prevent the intracellular biodegradation of iron oxide nanoflowers (Figure 2, Mazuel et al. Adv Funct Mat 2017) and thereby maintain their potential for magnetic hyperthermia, in addition to the excellent photothermal efficiency of the gold shell itself. Besides, it demonstrates that not only magnetic metrics, but also thermal ones can be quantitative mirrors of the intracellular status.



  • Mazuel F, Espinosa A, Radtke G, Bugnet M, Neveu S, Lalatonne Y, Botton GA, Abou-Hassan A, Wilhelm C. Magneto-Thermal Metrics Can Mirror the Long-Term Intracellular Fate of Magneto-Plasmonic Nanohybrids and Reveal the Remarkable Shielding Effect of Gold. Advanced Functional Materials, 27, 1605997 (2017).
  • Massive Intracellular Biodegradation of Iron Oxide Nanoparticles Evidenced Magnetically at Single Endosome and Tissue Levels. Mazuel F, Espinosa A, Luciani N, Reffay M, Le Borgne R, Motte L, Desboeufs K, Michel A, Pellegrino T, Lalatonne Y, Wilhelm C. ACS Nano, 10, 7627- 38 (2016)
  • Espinosa A, Curcio A, Cabana S, Radtke G, Bugnet M, Kolosnjaj-Tabi J, Péchoux C, Alvarez-Lorenzo C, Botton GA, Silva A, Abou-Hassan A, Wilhelm C. Intracellular Biodegradation of Ag Nanoparticles, Storage in Ferritin, and Protection by Au Shell for Enhanced Photothermal Therapy. ACS nano 12, 6523–6535 (2018)