Summary
The aim of this project is to elaborate biocompatible MNPs with maximized heating power and test them for cancer therapy via MH technique. The project includes the following objectives:
Objective 1: Elaboration and functionalization of ferrite MNPs with high hyperthermia capabilities:
Ferrite MNPs (MFe2O4, M=Co2+, Mn2+, and Zn2+) will be synthesized at high temperatures, in polyols of different molecular masses, increasing the boiling points of the solvents at high-pressure conditions. A systematic tuning of both the size and the morphology of MNPs by modifying the solvent/magnetic precursor ratio, the nature of polyol, the reaction time will be performed. The parameters will be selected in order to obtain mono-domain ferrite MNPs displaying the largest size below the superparamagnetic limit.
For the successful attachment of PEG molecules to the outer surface of the ferrite MNPs, a post-synthesis approach will be adopted. Modified PEG molecules, bearing different anchor groups as carboxylate, phosphate, and silane, which are able to bind covalently to the ferrite MNPs surface post-synthesized, will be used.
Objective 2. Biocompatibility, cellular uptake and toxicity assessment of the ferrite MNPs:
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In the present study, we aim to properly evaluate the characteristics of the MNPs at the moment of exposure, both qualitatively and quantitatively. Moreover, the possible interference of the synthesized MNPs with the biochemical tests used for the assessment of viability and oxidative stress will be investigated in order to assure that the results will reflect the cellular health as it is. The biocompatibility of the synthesized MNPs will be tested according to the recommendations of EU NanoSafety Cluster group by using 3 high-throughput complementary viability tests and as a gold standard the Trypan Blue staining. The cellular uptake will be quantified to evaluate the overall performance of the MNPs and a potential selectivity towards cancerous cells. In addition, the induction of oxidative stress and the disrupting effect of the ROS on the anti-oxidant cellular defense mechanisms will be of interest.
Objective 3. Magnetic hyperthermia capabilities assessment of ferrite MNPs:
The final objective of the project will be the evaluation of the applicability of the synthesized MNPs in MH. Non-cytotoxic doses for all MNPs will be further used for the MH.The concentrations at which the synthesized MNPs sufficiently accumulate in the different cell types and induce cellular death at temperatures not exceeding 45-46 °C will be further selected to evaluate if the cellular death is mediated via the apoptotic pathways. Microscopic images will be used to pinpoint the existence of the apoptotic bodies and of the overall apoptotic morphology of the cells undergoing this programmed cell death. The induction of oxidative stress, as a mechanism in the initiation of apoptosis, will also be evaluated.