MITHoS: Multimodal Innovative THeranostic nanoSystem
Novel, smart, personalized early diagnosis and therapies are urgently needed to treat cancer, which still represents one of the major causes of death worldwide with an increasing trend. We propose to develop a Multimodal Innovative THeranostic nanoSystem (MITHoS) to cover the gap between the present anticancer nanomedicine tools and the clinical requirements. Despite the intense research development of nanotheranostic tools, the deal with the complexity of these multi-component nanostructures in the biological environment is still an open challenge.
Nanotheranostic agents, which act at the same time for therapy and diagnosis, are based on the concerted actions of inorganic, organic and biological nanomaterials. Their effectiveness critically depends on the physico-chemical characteristics of their interfaces and on their behavior in physiological conditions and biological environment. When considering drug delivery nanosystems or therapeutic nanoparticles activated by the action of external stimuli, there is currently scarce understanding and control of the fundamental physical, chemical and biological processes that are involved. This gap of knowledge has so far impaired the translation of research efforts towards in vivo testing and finally to clinical practice.
MITHoS will be a hybrid theranostic nanosystem: an ultra-sound responsive core-shell nanoparticle, coupled to a pharmaceutically-relevant anticancer cargo, embedded in a cell-derived lipid bilayer shell and finally equipped by targeting ligands. MITHoS will be validated against multiple myeloma, a tumor for which relapses and disease progressions are common among affected patients, owing to innate or acquired drug resistance. It will overcome the limitations of the current approaches with a bottom-up strategy: on the foundations of new, fundamental knowledge concerning nano/bio interfaces, we will build a finely tuned, multi-purpose and time-controlled theranostic nanotool against cancer. We will use cutting-edge molecular simulation techniques to characterize all the involved nano/bio interfaces and develop predictive computational tools for the guidance of the experimental investigations. At the same time, the experimental synthesis, characterization and test of the MITHoS nanosystem will evolve from simple, model systems to more complex nanostructures employing a variety of forefront techniques, from high resolution microscopy to X-ray and neutron scattering, until the final goal of in-vivo testing of the MITHoS system. Furthermore, novel methodologies for stimuli-responsive and remotely-controlled diagnosis and therapy will be developed.
MITHoS concept will thus open new horizons in the nanomedicine field, proving how the synergic action of competences in the fields of physics, chemistry, material science, engineering, biophysics and biology can finally translate basic understanding into effective cancer treatment and overcome current barriers towards clinical translation.
This project has received funding from the Italian Ministry for Instruction, University and Research under the PRIN 2020 call with Decreto Direttoriale n.2284