The capability to modulate the activity of living cells with reversibility, high selectivity and spatio-temporal resolution, possibly in a minimally invasive way, is considered a major target in the biomedical technology field. In recent years, optical techniques have demonstrated the optimal capability to fulfil this objective. Huge extent has been directed towards optogenetics tools, thus requiring DNA cells viral transfer for light sensitization, which strongly slows the clinical tests. Light-sensitive smart materials, and in particular organic semiconductors, hold the potential to circumvent this major issue, acting as exogenous, biocompatible optical transducers. In this thesis, the synthesis of a novel, low band-gap conjugated polymer in the form of nanoparticles is reported. Polymer beads are prepared in sterile conditions and dissolved in biological media. Their optical and electronic properties are characterized in detail. Secondary line cell models have been then treated with polymer NPs. The latter easily internalize within the cell cytosol and are highly biocompatible. Finally, the functional interaction between living cells and NPs upon optical excitation has been studied by ion imaging experiments. Interestingly, this work demonstrates that the photo-electrochemical activity of polymer beads actively modulates the intracellular Reactive Oxygen Species concentration, while not sizably affecting the intracellular Ca2+ dynamics and cell viability. Reported results are interesting in view of further exploitation of optical modulation of ROS balance for novel therapeutic approaches.
La capacità di modulare l’attività di cellule viventi in modo reversibile e con elevata selettività e risoluzione spazio-temporale, possibilmente in modo non invasivo, è una delle principali line di ricerca nel campo della tecnologia biomedica. Negli ultimi anni, le tecniche ottiche sono emerse come ottime candidate per il raggiungimento di questo obiettivo. Sfortunatamente, sono basate principalmente su approcci optogenetici, che richiedono la modificazione genetica del DNA delle cellule. Un approccio alternativo a questo problema è offerto da materiali innovativi sensibili alla luce, in particolare semiconduttori organici, altamente biocompatibili e in grado di agire da trasduttori ottici. In questa tesi è mostrato il processo di fabbricazione di nanoparticelle di un polimero coniugato a basso band gap. Le nanoparticelle sono preparate in condizioni sterili e disperse in mezzi biologici. Le loro proprietà ottiche ed elettroniche sono caratterizzate in dettaglio. Le nanoparticelle polimeriche sono state somministrate in vitro a linee cellulari secondarie. Quest’ultime sono facilmente internalizzate nel citosol cellulare e sono altamente biocompatibili. Infine, l’interazione funzionale tra cellule viventi e nanoparticelle mediata da eccitazione ottica è stata studiata con esperimenti di imaging. Questo lavoro dimostra che l’attività fotoelettrochimica delle nanoparticelle polimeriche modula efficacemente la concentrazione delle specie reattive dell’ossigeno, mentre non sono stati riscontrati effetti significativi sulle dinamiche di ioni Ca2+. I risultati riportati offrono interessanti prospettive in vista di un futuro utilizzo di nanoparticelle organiche come modulatori ottici delle concentrazioni di specie reattive dell’ossigeno in innovativi approcci terapeutici.
PCPDTBT-based nanoparticles as smart photoactive transducers in cellular metabolism
GOBBO, FEDERICO
2017/2018
Abstract
The capability to modulate the activity of living cells with reversibility, high selectivity and spatio-temporal resolution, possibly in a minimally invasive way, is considered a major target in the biomedical technology field. In recent years, optical techniques have demonstrated the optimal capability to fulfil this objective. Huge extent has been directed towards optogenetics tools, thus requiring DNA cells viral transfer for light sensitization, which strongly slows the clinical tests. Light-sensitive smart materials, and in particular organic semiconductors, hold the potential to circumvent this major issue, acting as exogenous, biocompatible optical transducers. In this thesis, the synthesis of a novel, low band-gap conjugated polymer in the form of nanoparticles is reported. Polymer beads are prepared in sterile conditions and dissolved in biological media. Their optical and electronic properties are characterized in detail. Secondary line cell models have been then treated with polymer NPs. The latter easily internalize within the cell cytosol and are highly biocompatible. Finally, the functional interaction between living cells and NPs upon optical excitation has been studied by ion imaging experiments. Interestingly, this work demonstrates that the photo-electrochemical activity of polymer beads actively modulates the intracellular Reactive Oxygen Species concentration, while not sizably affecting the intracellular Ca2+ dynamics and cell viability. Reported results are interesting in view of further exploitation of optical modulation of ROS balance for novel therapeutic approaches.File | Dimensione | Formato | |
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https://hdl.handle.net/10589/145699