Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - ICARO (Colloidal Inorganic Nanostructures for Radiotherapy and Chemotherapy)

Teaser

The goal of ICARO is to develop a nanocrystal (NC) platform to merge radio and chemotherapy into a single entity that acts more specific towards tumor cells. Our goal is to establish protocols for the preparation of radiolabelled-NCs that will be easily translated to the...

Summary

The goal of ICARO is to develop a nanocrystal (NC) platform to merge radio and chemotherapy into a single entity that acts more specific towards tumor cells. Our goal is to establish protocols for the preparation of radiolabelled-NCs that will be easily translated to the medical practice for radiotherapy. In particular, our objective is to develop heterostructures that will combine radio and chemotherapy, the latter of which is based on the use of magnetic nanoparticles that can trigger drug release under exposure to an alternating magnetic field (AMF). The radiotherapy will be based on the insertion of radionuclides on semiconductor nanocrystals. During this first part of the project, we have started to develop magnetic nanoparticles and heterostructures that have optimized heat performances under AMF. This is crucial in order to reduce the dose of magnetic material and to exploit the heat to efficiently activate the release of drug molecules that are associated to the particles.

Work performed

To this aim, we have been working on the synthesis of gold-iron oxide heterostructures with enhanced heat performances. By controlling the size of the magnetic domain in the range between 18 and 28 nm, we have identified the size range of of 23-25 nm as being the most suitable one to have enhanced heat efficiency under AMF( (P. Guardia et al., J. Mater. Chem. B, 2017,202f5, 4587-4594). This heterostructure will be further used as an intermediate nanoplatform to grow semiconductor nanocrystals.
We have also studied, in more detail, the mechanism by which magnetic iron oxide and cobalt-based ferrite nanocubes heat under AMF. By performing magnetic characterization (i.e. hysteresis curves) and calorimetric measurements under AMF conditions in media at different viscosities, we have found that small nanocubes are less susceptible to variation in their heat efficiency than larger cubes when changing the viscosity of the environment in which they are present. However, absolute specific absorption rate (SAR) values (a parameter that measures the heat ability of magnetic nanoparticles under AMF) are generally lower for smaller nanocubes than for bigger ones (D. Cabrera et al, Nanoscale, 2017, 9, 5094-5101). This finding needs to be taken into consideration when thinking about the application of magnetic nanoparticles to viscous environments, like that of a tumor or sub-compartments of tumor cells.
In another study we focused on correlating the variation of the heat efficiency of magnetic nanoparticles when exposed to different treatments. For instance, on core/shell structures with different phases of iron oxide (made of an FeO core in a shell of Fe3O4), we found that we can improve the SAR values of the sample by applying AMF. When applying this mild AMF magnetic stimulation approach, the heat performances reached were very similar to the ones obtained when exposing magnetic nanoparticles to high temperatures (A. Lak et al., Scientific report, 2016, s 6, 33295).
We have also focused on developing a procedure to stabilize semiconductor nanocrystals in the aqueous phase. For instance, we transferred colloidal CuFeS2 nanocrystals to water and studied the physical-chemical properties and the in vitro characterization of the water transferred nanoparticles (S. Goash, Chem. Mater., 2016, 28 (13), 4848–4858). We are now proceeding with setting protocols for radioisotope insertions on various semiconductor nanocrystals including CuFeS2 nanocrystals.

Final results

The project ICARO is now proceeding accordingly to the planned activities and to date very promising results in the field of developing new protocols for the radiolabeling of inorganic nanocrystals have been achieved going beyond the state of the art. A few publications are in preparation.
We are also advancing the field of magnetic hyperthermia either by developing new magnetic nanoparticles and their clusters with optimized heat efficiency or by setting magnetic nanomaterials that can mantain unchanged heat efficiency when located intracellularly or at the interstitial space at the tumor.
We are also progressing with drug delivery study and we found that when loading doxorubicin on thermo-responsive polymeric iron oxide nanocubes do not release drugs in conditions of local magnetic hyperthermia. This result deserves further studies as few other groups have found opposite behavior with thermo-responsive systems at different compositions.