Over the last decade, promising results have been obtained in the study and the research of block copolymers, finding an innovative method for creating them, according to a process of synthesis through self-assembly, known as Polymerization-Induced Self-Assembly (PISA). The use of self-assembled copolymers varies in different fields, but the one that in the last years has been the main research point is the one related to the delivery and release of small molecules for medical purposes. Initially, the most widespread methods for initializing polymerization processes were based on thermal systems. Recently, studies of PISA processes initialized by visible light (Photo-PISA) have offered many advantages for the synthesis processes. This method allows to obtain a high degree of control, temporal and spatial, during the polymerization process, through the manipulation of wavelengths and intensities of the light. This master thesis focuses on the study, the synthesis and the characterization of polymeric nanoparticles obtained through PET-RAFT polymerization of 2-(methylthio)ethyl methacrylate (MTEMA), using ZnTPP, a water-soluble zinc derivative, as photocatalyst. The synthesis process was carried on by irradiating the sample with red light (λmax = 595 nm). Two coumarin monomers with different reactivity with MTEMA were used. Using the same light for the synthesis or the blue light (λmax = 470 nm), the disassembly process can be activated; this can be done because the thiolether can be oxidised by the oxygen singlet converted by the ZnTPP, turning it into sulfoxide (hydrophobic). Thanks to the coumarin monomer it was possible to induce the crosslinking of the particles by irradiating it with UV light (λmax = 365 nm). The process of dimerization was then inverted by using a shorter wavelength UV light (λmax = 254 nm). To understand the behaviour of the nanoparticles obtained during the different stages, the evolutions of the size, of the molecular weight and of the conversion rate were studied through DLS, DPC and 1H-NMR and afterwards it was confirmed by the TEM images. The collected data showed promising results in the field of drug delivery (crosslinking) and drug release (disassembly and decrosslinking), particularly for one of the two coumarin monomers. All these processes were performed using visible light of different wavelengths, confirming an easy control and a great energetic efficiency of the Photo-PISA synthesis processes. Drug loadings and bio-tests could be performed in the future to prove the potential of these nanoparticles so that they can be used for bio-applications.
Nel corso dell’ultimo decennio, sono stati ottenuti promettenti risultati nello studio e nella ricerca di copolimeri a blocchi, trovando un innovativo metodo per poterli creare, attraverso un processo di sintesi tramite self-assembly conosciuto come Polymerization-Induced Self-Assembly (PISA). L’utilizzo di self-assembled copolimeri spazia in diversi campi, ma quello che negli ultimi anni è stato il principale punto di ricerca è quello relativo al trasporto e al rilascio di piccole molecole a scopo medico. Inizialmente, i metodi più diffusi per inizializzare i processi di polimerizzazione si fondavano su sistemi termici. Più recentemente, studi sui processi PISA inizializzati da luce visibile (Photo-PISA) hanno portato numerosi vantaggi ai processi di sintesi. Questo metodo consente di ottenere un alto grado di controllo, temporale e spaziale, durante il processo di polimerizzazione, attraverso la manipolazione di lunghezze d’onda e intensità della luce. Questa tesi magistrale si concentra sullo studio, sulla sintesi e sulla caratterizzazione di nanoparticelle polimeriche ottenute attraverso polimerizzazione PET-RAFT di 2-(methylthio)ethyl methacrylate (MTEMA), utilizzando ZnTPP, derivato di zinco solubile in acqua, come fotocatalizzatore. Il processo di sintesi è stato condotto irradiando i campioni con luce rossa (λmax = 595 nm). Sono stati utilizzati 2 monomeri di cumarina con differenti reattività con MTEMA. Utilizzando la stessa luce per la sintesi delle particelle o la luce blu (λmax = 470 nm), il processo di disassembly può essere attivato; questo perché il tioetere può venir ossidato dal singoletto di ossigeno precedentemente convertito dal ZnTPP, trasformandolo in solfossido (idrofobico). Grazie al monomero di cumarina è stato possibile indurre il crosslinking delle nanoparticelle, irradiandole con luce UV (λmax = 365 nm). Il processo di dimerizzazione è stato poi invertito utilizzando luce UV di minore lunghezza d’onda (λmax = 254 nm). Per comprendere il comportamento delle diverse nanoparticelle ottenute nei vari passaggi, l’evoluzione della dimensione, del peso molecolare e del tasso di conversione è stata studiata attraverso DLS, GPC e 1H-NMR e successivamente confermata dalle immagini al microscopio TEM. I dati ottenuti hanno indicato promettenti risultati nell’ambito della drug delivery (crosslinking) e della drug release (disassembly e decrosslinking), soprattutto per uno dei 2 monomeri di cumarina. Tutti questi processi sono stati realizzati utilizzando luce visibile a diverse lunghezze d’onda, confermando un facile controllo e una notevole efficienza energetica dei processi di sintesi Photo-PISA. Drug loading e bio-test potranno venir effettuati successivamente per dimostrare il potenziale di queste nanoparticelle al fine di poter essere utilizzate in applicazioni biologiche.
Photoinitiated polymerization-induced self-assembly (Photo-PISA) of MTEMA
BOZZINI, LUCA
2018/2019
Abstract
Over the last decade, promising results have been obtained in the study and the research of block copolymers, finding an innovative method for creating them, according to a process of synthesis through self-assembly, known as Polymerization-Induced Self-Assembly (PISA). The use of self-assembled copolymers varies in different fields, but the one that in the last years has been the main research point is the one related to the delivery and release of small molecules for medical purposes. Initially, the most widespread methods for initializing polymerization processes were based on thermal systems. Recently, studies of PISA processes initialized by visible light (Photo-PISA) have offered many advantages for the synthesis processes. This method allows to obtain a high degree of control, temporal and spatial, during the polymerization process, through the manipulation of wavelengths and intensities of the light. This master thesis focuses on the study, the synthesis and the characterization of polymeric nanoparticles obtained through PET-RAFT polymerization of 2-(methylthio)ethyl methacrylate (MTEMA), using ZnTPP, a water-soluble zinc derivative, as photocatalyst. The synthesis process was carried on by irradiating the sample with red light (λmax = 595 nm). Two coumarin monomers with different reactivity with MTEMA were used. Using the same light for the synthesis or the blue light (λmax = 470 nm), the disassembly process can be activated; this can be done because the thiolether can be oxidised by the oxygen singlet converted by the ZnTPP, turning it into sulfoxide (hydrophobic). Thanks to the coumarin monomer it was possible to induce the crosslinking of the particles by irradiating it with UV light (λmax = 365 nm). The process of dimerization was then inverted by using a shorter wavelength UV light (λmax = 254 nm). To understand the behaviour of the nanoparticles obtained during the different stages, the evolutions of the size, of the molecular weight and of the conversion rate were studied through DLS, DPC and 1H-NMR and afterwards it was confirmed by the TEM images. The collected data showed promising results in the field of drug delivery (crosslinking) and drug release (disassembly and decrosslinking), particularly for one of the two coumarin monomers. All these processes were performed using visible light of different wavelengths, confirming an easy control and a great energetic efficiency of the Photo-PISA synthesis processes. Drug loadings and bio-tests could be performed in the future to prove the potential of these nanoparticles so that they can be used for bio-applications.File | Dimensione | Formato | |
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https://hdl.handle.net/10589/148933