Designing and monitoring all the preparation steps of a drug delivery system is essential to achieve a specific target. Each part of a nanocarrier affects the batch itself and the surrounding environment. In addition, to obtain monodispersed samples, the coating and any functionalization are crucial to determine the colloidal stability, to predict the behavior with a biological system, and the reaching of the target site. In particular, the achievement of intracellular sites by rationalizing the internalization mechanisms and quantifying the carriers in the target is still today a hot topic in the nanomedical field. Here, a class of multidentate polymers was presented: a simple way to synthesize them and show their broad applicability in combination with metal NPs. Multi-branched polymers were involved in three projects. The first project aimed to present a multidentate polymer as a general model to be applied in the coating of metal surfaces. To prove this, several tests were carried out by modulating the composition and size of the NPs. This easily synthesized polymer has been compared with two types of coatings common in literature. The obtained data show how the new surfactant provides high colloidal stable nanoparticles. Secondly, this leads to improvements from the point of view of toxicity and bio-functionalization. In the second project, the ligands polymer chain was modified to increase the range of application. Moreover, the choice of the ligand was based on the affinity for certain metal surfaces. In this case, the molecule is 4-aminotiophenol which is often used for SERS applications. Initially, the versatility of the polymer was investigated by coating different types of metallic NPs (gold and silver) and then SERS analyses were performed. Size and shape played a key role, especially with cubic concave nanoparticles that are promising for diagnostics application. In the second part of the project, cubic silver nanoparticles were used as a model for the evaluation of cell trafficking and endosomal maturation. Preliminary tests of NPs have been carried out at different pH (to emulate the pH variations in the endosomal evolution stages) and in vitro studies to check the nanoparticles uptake in HeLa cells were performed. The third project aimed to use the designed polymer as precursor in the synthesis of anisotropic nanoparticles. The shape obtained is a petal form. Subsequently, with the increase of the temperature, the petals assembled to nanoflowers above 100 nm. The presence of the active SERS polymer makes these nanoparticles, excellent candidates for this application.

È fondamentale progettare e monitorare tutte le fasi preparative di un sistema di drug delivery in modo tale da raggiungere un determinato sito bersaglio. Ogni parte di un nanocarrier influenza sé stesso e l'ambiente circostante. Inoltre, per ottenere campioni monodispersi, il rivestimento e le eventuali funzionalizzazioni sono fondamentali per determinare la stabilità colloidale, prevedere il comportamento in un sistema biologico e raggiungere il target di interesse. In particolar modo, la razionalizzazione dei meccanismi di internalizzazione e la quantificazione dei carrier nei siti intracellulari è ancora oggi un tema di grande interesse in ambito nanomedico. In questo lavoro, è stata presentata una classe di polimeri multidentati di facile sintesi mostrando un'ampia applicabilità in combinazione con nanoparticelle (NPs) metalliche. I polimeri multidentati sono stati coinvolti in tre diversi progetti. Il primo progetto mirava a presentare un polimero multidentato come modello generale da applicare nel rivestimento di superfici metalliche. Per dimostrarlo sono stati effettuati diversi test prendendo in considerazione la composizione e la dimensione delle NPs. Questo polimero è stato confrontato con altri due tipi di rivestimenti comuni in letteratura. I dati ottenuti mostrano come il nuovo rivestimento fornisca una maggiore stabilità colloidale. In secondo luogo, sono stati ottenuti miglioramenti dal punto di vista della tossicità e della bio-funzionalizzazione. Nel secondo progetto, la catena polimerica è stata modificata con un altro ligando per ampliare il campo di applicazione di questi polimeri. La scelta della molecola è basata sull'affinità per alcune superfici metalliche. In questo caso la molecola scelta è il 4-amminotiofenolo, spesso utilizzata per applicazioni SERS. Inizialmente, il polimero è stato studiato rivestendo diversi tipi di NPs metalliche (oro e argento) e sono state eseguite analisi SERS. Le dimensioni e la forma hanno giocato un ruolo chiave, in particolare con le nanoparticelle cubiche concave risultando promettenti agenti diagnostici. Nella seconda parte del progetto, le nanoparticelle cubiche d'argento sono state utilizzate come modello per la valutazione del traffico cellulare e della maturazione endosomiale. Dei test preliminari sono stati effettuati a diversi pH (per emulare le variazioni di pH nelle fasi evolutive dell'endosoma) e studi in vitro sono stati eseguiti per verificare l'uptake delle NPs nelle cellule HeLa. Il terzo progetto mirava a utilizzare il polimero sintetizzato come precursore nella sintesi di nanoparticelle anisotropiche. La forma ottenuta inizialmente è stata quella di un petalo, ma aumentando la temperatura, i petali si sono assemblati a nanofiori con un diametro al di sopra di 100 nm. La presenza del polimero SERS-attivo rende queste nanoparticelle ottimi candidati per questa tipologia di applicazione.

(2022). Synthesis of multi-branched polymers for the stabilization of metallic nanoparticles. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2022).

Synthesis of multi-branched polymers for the stabilization of metallic nanoparticles

GIUSTRA, MARCO DAVIDE
2022

Abstract

Designing and monitoring all the preparation steps of a drug delivery system is essential to achieve a specific target. Each part of a nanocarrier affects the batch itself and the surrounding environment. In addition, to obtain monodispersed samples, the coating and any functionalization are crucial to determine the colloidal stability, to predict the behavior with a biological system, and the reaching of the target site. In particular, the achievement of intracellular sites by rationalizing the internalization mechanisms and quantifying the carriers in the target is still today a hot topic in the nanomedical field. Here, a class of multidentate polymers was presented: a simple way to synthesize them and show their broad applicability in combination with metal NPs. Multi-branched polymers were involved in three projects. The first project aimed to present a multidentate polymer as a general model to be applied in the coating of metal surfaces. To prove this, several tests were carried out by modulating the composition and size of the NPs. This easily synthesized polymer has been compared with two types of coatings common in literature. The obtained data show how the new surfactant provides high colloidal stable nanoparticles. Secondly, this leads to improvements from the point of view of toxicity and bio-functionalization. In the second project, the ligands polymer chain was modified to increase the range of application. Moreover, the choice of the ligand was based on the affinity for certain metal surfaces. In this case, the molecule is 4-aminotiophenol which is often used for SERS applications. Initially, the versatility of the polymer was investigated by coating different types of metallic NPs (gold and silver) and then SERS analyses were performed. Size and shape played a key role, especially with cubic concave nanoparticles that are promising for diagnostics application. In the second part of the project, cubic silver nanoparticles were used as a model for the evaluation of cell trafficking and endosomal maturation. Preliminary tests of NPs have been carried out at different pH (to emulate the pH variations in the endosomal evolution stages) and in vitro studies to check the nanoparticles uptake in HeLa cells were performed. The third project aimed to use the designed polymer as precursor in the synthesis of anisotropic nanoparticles. The shape obtained is a petal form. Subsequently, with the increase of the temperature, the petals assembled to nanoflowers above 100 nm. The presence of the active SERS polymer makes these nanoparticles, excellent candidates for this application.
COLOMBO, MIRIAM
Polimeromultidentato; Stabilità colloide; SERS; Stadi endosomaiali; NPs anisotropiche
Multidentate polymer; Colloidal stability; SERS; Endosomal maturation; NPs anisotropiche
CHIM/04 - CHIMICA INDUSTRIALE
English
17-feb-2022
SCIENZA E NANOTECNOLOGIA DEI MATERIALI
34
2020/2021
embargoed_20250217
(2022). Synthesis of multi-branched polymers for the stabilization of metallic nanoparticles. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2022).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/366171
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