Technology Readiness Levels (TRL) at the beginning of the project

 

Level 1- Basic principles observed and reported:

• Iron Oxide Magnetic Nanoparticles do deliver heat upon exposure to external AC magnetic field.

• Iron Oxide Magnetic Nanoparticles do exhibit no-toxicity up to a concentration of 0.2 mg/ml.

• Iron Oxide Magnetic Nanoparticles can be internalized in all types of cancer cells.

 

Level 2 - Technology concept and/or application formulated:

• The synthesis method developed by our group is capable to deliver polyhedral Iron Oxide Magnetic Nanoparticles with high heating capabilities – around 2000 W/gFe near the safety limit.

• The polyhedral IOMNPs exhibit almost no toxicity for the concentration range up to 0.2 mg/ml as indicated by the MTT assays performed on four cell lines.

• The polyhedral IOMNPs penetrated the cells through endocytosis, in a time-dependent manner, accumulating in endosomes in a large amount.

 

Consequently, the potential application of polyhedral IOMNPs

for magnetic hyperthermia is validated.

 

References:

1. Iacovita, C. et al. Polyethylene glycol-mediated synthesis of cubic iron oxide nanoparticles with high heating power, Nanoscale Res. Lett., 2015, 10, 1–16.

2. Iacovita, C. et al. Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties. Molecules, 2016, 21(10), 1357(1) – 1357(21).

3. Radu, T., Iacovita. C, et al. X-Ray Photoelectron Spectroscopic Characterization of Iron Oxide Nanoparticles, Applied Surface Science, 2017, 405, 337–343.

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Technology Readiness Levels (TRL) reached after project implementation

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Level 3 - Analytical and experimental critical function and/or characteristic proof-of-concept:

• We propose to firstly improve the biocompatibility of polyhedral iron oxide MNPs by coating them with a shell of silica (or PEG)

• Secondly, by doping of iron oxide MNPs with transition metal ions (zinc, manganese and cobalt) and increasing the synthesis temperature above the boiling point of the solvent, their magnetic properties will  be significantly improved leading to a enhancement of their heating performances

• Silica or (PEG) shell around iron oxide MNPs will lead to the internalization of large amounts of iron oxide MNPs inside cancer cells.

• Silica (or PEG) shell around iron oxide MNPs will reduce the inter-particle dipole-dipole interactions leading to a maximization of their heating capabilities.

• The magnetic hyperthermia experiments on different types of cancer cells will demonstrate the capability of silica (or PEG) coated iron oxide MNPs to induce apoptosis, at concentration bellow their intrinsic toxicity and in the safety limit of AC magnetic fields.

 

 

Consequently, the predicted capabilities of polyhedral iron oxide MNPs for magnetic hyperthermia assays are demonstrated by in vitro experiments. The objectives of the three R’s principle

(replacement, reduction, refinement [of animal experiments]) are fulfilled

and the product can be promoted to the next level

consisting on animal experiments.