Hybrid Nano-systems Based on PEGylate Porphyrins: Synthesis, Characterization and Theranostic Applications

Following the modern lines of development in theranostic field, this PhD research project focuses mainly on the field of oncological therapies where the primary purpose of the research is to increase the effectiveness of treatments and to decrease the undesirable toxic side effects of current therapies, which indiscriminately affect both sick and healthy cells, causing often serious collateral damages. The goal can be achieved by creating biocompatible smart systems that do not require carriers to function, but that are themselves able to "move" recognize and treat diseased tissues. The research project proposes the development of new organic/inorganic hybrid nanosystems having a core-shell-shell structure, consisting of nanoparticles (NPs) (Au and/or Fe3O4@Au) in which PEGylate porphyrin systems are bounded. The choice of synthesizing these hybrid systems, stems from the possibility of exploiting the different properties of the individual components, combined into a single complex system. The gold nanoparticles were chosen for the different properties in the theranostic field. AuNPs are considered to be relatively biologically non-reactive and therefore suitable for in vivo applications. Other advantageous qualities include the strong optical properties of AuNPs due to localized surface plasmon resonance (LSPR), easily controllable surface chemistry which enables versatility in adding surface functional groups, and lastly, the ease in control over particle size and shape during synthesis. Silver nanoparticles (AgNPs) are increasingly being investigated as tools for novel cancer therapeutics, capitalizing on their unique properties to enhance potential therapeutic efficacy. The AgNPs are a promising tool as anticancer agents in diagnostics and probing, with strong effects against different cancer cell lines offering many advantages. Their better penetration, and the possibility to track AgNPs in the body make them a more efficient tool in cancer treatment with less risk compared to standard therapeutic procedures. The unique AgNP properties, such as easy surface functionalization, optical properties, reproducible synthetic routes and high surface: volume ratio, makes them suitable for cancer treatment. The optical properties can be tuned to have an absorption at specific wavelengths that is useful for imaging and photothermal applications in tissue. The magnetite core will provide the paramagnetic properties necessary for use in the Targeted Drug Delivery (NPs tissues via magnetic field), in Magnetic Resonance Imaging and Magnetic Hyperthermia (the magnetic NPs may be subjected to an alternating magnetic field, overheating and thus determining cell death). The nanoscale dimensions of the complex system (40-100 nm) will allow the latter to perform passive targeting (EPR effect), while the external shell obtained by functionalization with the PEGylated porphyrins derivatives will induce the necessary water solubility and biocompatibility of the whole system. Given the excellent absorption spectroscopic properties, fluorescence (to monitor its presence inside the tissues) and photo-cytotoxicity (for the photodynamic therapy of tumors), it will be possible to strongly implement the field of application and efficiency of these nanohybrid systems. In synthesis, upon validation of the functioning of the system, the synthesis strategy can be adapted to functionalize and/or co-functionalize the nanoparticles also with active targeting agents to limit the accumulation exclusively in diseased tissues endowed with specific receptors, further implementing the targeting properties described above. Therefore, the results obtained during my PhD research work, could be a fundamental starting point in order to developing systems for theranostic applications, exploiting both the nanoparticles and the porphyrin derivatives properties, thus to obtain multifunctional platforms for biomedical applications.