In last decade nanomaterials have been widely explored in developing field of nanotechnology and nanomedicine. The size-dependent properties of nanomaterials make them particularly suited for advanced applications and a fine tuning of the physical-chemical characteristics is possible by a proper choice of the material, size and surface functionalization.
The objective of this study will be focused on the study of functionalized metal nanoparticles (MNPs) and nanostructured polymers (NPOLY), in particular for drug delivery and for applications in nuclear medicine and radiotherapy. In this framework, this project will be also focused on the development of detector systems for in vivo real-time radiation detection. One of such detectors is at the level of first clinical tests and is proposed to evolve to cover also dosimetry for Targeted Radio-Therapy. The project will be developed thanks to the multi-disciplinary skills of the participants, ranging from inorganic chemistry, physics, biophotonics and optoelectronics.
MNPs (M = Au, Ag) will be prepared by wet chemical reduction in the presence of different thiols and NPOLY will be prepared with radical polymerization in emulsion conditions, starting from vinyl monomers. Selected dyes, drugs and bioactive agents will be immobilized onto the MNPs and NPOLY surfaces. In particular, polymeric MNPs and NPOLY will be allowed to interact with Y3+ salt containing a source of Yttrium-89 as a model for Yttrium-90 a ß- emitting radioisotope. This specific target has been selected in the framework of a well assessed collaboration on radio-guided surgery.
MNPs and NPOLY and their derivatives will be deeply characterized to obtain information on composition, surface functionality and structure-property relationship. Optothermal and photoacoustic spectroscopies will be used to have spatial information about the optical absorption for local heating, fundamental starting point for biophotonics and nanomedicine studies.
The research topic on the design of new nanostructured materials, aimed to technological and biomedicine applications is one of the crucial area of research and of great strategic importance, also included into the Horizon 2020 program for the priority of Advanced Materials in Emerging Technologies (PE5. Synthetic Chemistry and Materials: Materials synthesis, structure-properties relations, functional and advanced materials, molecular architecture, organic chemistry). The design and study of new materials is based on an interdisciplinary approach and a close collaboration between researchers from different scientific fields is of fundamental importance. On these basis and supported by the international framing of the research programs, this project will be developed by a multi-disciplinary approach, based on complementary skills of the participants ranging from inorganic chemistry, physics, optoelectronics to biophotonics.
The innovation represented by this project is on the preparation of new materials, i.e. MNPs stabilized with organic or organometallic thiols and NPOLY based on vinyl monomers, and their use in in optoelectronics and biomedicine fields. The synthetic procedures for AuNPs will be applied to less explored metals, such as Ag, Pt and Pd. Hydrophobic and hydrophilic thiols will be chosen and introduced as single or mixed layers. The use of mixed ligands represents a challenging objective, still not deeply explored in the literature. Among others, dithiols will be used. These latter dithiols are really peculiar and new in the state of the art, with the potential to drive the self assembly of 2D or 3D ordered arrays. In these systems conductivity measurements represent a challenging objective aimed to investigate the electronic levels of MNPs and their potentiality in optoelectronics.
nPOLY will be prepared with mean size in the range 50-500 nm and this represent an innovation with respect to the state of the art, where nPOLY are often used with sizes more than 200 nm. The inclusion of bioactive molecules represents an innovative and really up to date objective that can be achieved thanks a bottom up approach. The loading, stability and release studies are of fundamental interest for nanobiotechnology studies and the proper choice of surface functionalities allow for example to immobilize hydrophobic biomolecules onto highly hydrophilic NPs. The use of NPs as drug delivery systems is one of the emerging field of nanomedicine and have a great potential impact on the development of new knowledge. The use of hydrophilic NPs can in fact be fundamental for the delivery of drugs with low solubility.
Optical studies based on photoacoustic and photothermal spectroscopies will allow to evaluate the optothermal properties such as thermal diffusivity, optical absorption independently from the scattering of the NPs based systems.
The development of the innovative RGS technique represents a break-though in nuclear medicine, as it has been stressed by a press release of the American Society of Nuclear Medicine (SNMMI -- http://home.infn.it/?option=com_content&view=article&id=630:elettroni-pe... ). The developed device, patented at 75% by Sapienza (PCT/IT2014/000025), requires a last effort to make the leap from research to industrial application. Similarly the development of new radio-tracers is a field that is required for appropriate efficacy of nuclear medicine, but very few groups work on it in Europe. Building and supporting a team able to develop a radio-tracer from its synthesis to preclinical tests is a huge contribution to nuclear medicine. The highly multidisciplinary team involved in this project have the expertise and are developing the tools to be cover such a role.
As far as dosimetry in TRT is concerned, the proposed technique is completely innovative and fills a gap that has recently become important at European level, since it has been acknowledge the need for personalized estimates (European Directive 2013/59/EURATOM).
The development of this project consists of approximately 36 months. In a preliminary phase of 6-12 months the synthesis of MNPs and nPOLY pristine and in the presence of bioactive molecules will be carried out together with a their preliminary spectroscopic characterization (12 months). In a latter phase, selected and well defined systems will be used for fine characterizations and applicative tests.
The main element for the evaluation of the quality of the results lies in their dissemination and publication in international scientific journals with high impact factors. The participants in this research project therefore intend to submit their results to the scientific community through conferences and scientific journals. The participants are also involved in national and international research project applications.