Two kind of multifunctional theranostic platforms that prevent agglomeration among MNPs have been successfully fabricated by 2 different methods:
1) Wet-chemical synthesis: A surface modification of MNPs with Poly(maleic anhydride-alt-1-octadecene)-grafted Poly(ethylene glycol) copolymer (PMAO-PEG) in order to achieve single-particle polymer coatings. In this configuration, MNPs present minimal dipolar interactions. (Platform I)
2) Microfabrication: A homogeneous and controlled assembly of MNPs within polymeric-inorganic microdisks fabricated by photolithography. The monolayer of MNPs are immobilized within a polymeric multilayer, so clustering effects are significantly reduced. (Platform II)
In the following the most relevant achievements will be listed:
-Fine control over several physicochemical properties has been achieved in both platforms (size, morphology, composition, crystallinity, etc.).
-Highly reproducible and efficient magnetothermal performance have been achieved in physiological media and in-vitro.
-By controlling several conjugation parameters (the amount of reagents, reaction time, inert atmosphere, etc.), it has been possible to tailor the MNP-Ab system between 5-15 Ab/NP.
-It has been possible to tailor the arrangement of MNPs within platform II in different configurations:
i) When MNPs are sprayed in specific conditions and in absence of an external magnetic field, 2D assemblies with minimal agglomeration degree and with the magnetic moments randomly oriented are achieved
ii) Otherwise, when the MNPs are sprayed in the same conditions but under a permanent magnetic field of 245 mT, the MNPs are assembled in oriented patches.
The coercivity (Hc) at RT of the randomly oriented assembly does not change when the measurement is performed at 0º or 90º with respect to the magnetic field. On the contrary, the Hc of oriented assembly is significantly higher when measured at 0º. This indicates an increase of the shape anisotropy in this kind of 2D arrays, which very likely will lead to larger SLP values.
-The design and refinement of a magneto-optic system has been performed based on platform I. This platform is not only an efficient magneto-fluorescent marker, but also a highly suitable system to track the magnetic hyperthermia treatment locally.
-Toxicity assays in-vitro have revealed that platform I and II are completely biocompatible. In addition, it has been demonstrated the great endocytosis resistance of these systems.
- Highly efficient magnetic hyperthermia in-vitro (in colon cancer-derived cell line (HCT116) ) was achieved using low/modarate concentration of MNPs out at 17 kA/m and 650 kHz. Two different nanoparticle concentrations were used (C1=0.25 and C2=0.5 mg/ml) and the determined initial heating rate was 2 ºC/min and 4 ºC/min, respectively. The magnetic field was applied for one hour and the cells with NPs reached 48 and 44 ºC, while the control stayed at the T of the background. And 48 h post-hyperthermia a complete cell death was achieved when using C2. Although the decrease in cell number for C1 was not statistically significant, the expression of apoptosis genes (BCL10 and CASP8) was enhanced, meaning that the apoptotic process had been already activated and they would die within a short period of time.
