Dal Poggetto, Giovanni (2020) Supramolecular chemistry: realization of multifunctional nanoparticles. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Resource language: English
Title: Supramolecular chemistry: realization of multifunctional nanoparticles
Creators:
CreatorsEmail
Dal Poggetto, Giovannigiovanni.dalpoggetto@unina.it
Date: 11 March 2020
Number of Pages: 169
Institution: Università degli Studi di Napoli Federico II
Department: Ingegneria Chimica, dei Materiali e della Produzione Industriale
Dottorato: Ingegneria dei prodotti e dei processi industriali
Ciclo di dottorato: 32
Coordinatore del Corso di dottorato:
nomeemail
Mensitieri, Giuseppemensitie@unina.it
Tutor:
nomeemail
Ambrogi, VeronicaUNSPECIFIED
Laurienzo, PaolaUNSPECIFIED
Date: 11 March 2020
Number of Pages: 169
Keywords: drug-delivery; nanoparticles; self-assembly
Settori scientifico-disciplinari del MIUR: Area 03 - Scienze chimiche > CHIM/05 - Scienza e tecnologia dei materiali polimerici
Area 03 - Scienze chimiche > CHIM/07 - Fondamenti chimici delle tecnologie
Date Deposited: 22 Mar 2020 23:36
Last Modified: 10 Nov 2021 10:03
URI: http://www.fedoa.unina.it/id/eprint/13061

Collection description

Development of nanotechnology in medicine, and more precisely drug delivery, has provided attractive options for therapy of a wide variety of tumors. Chemotherapeutic agents have often undesired properties (e.g. poor solubility and selectivity) To overcome these issues, one of the most promising strategy consists in loading drugs in nanocarriers. Nanocarriers can be specifically designed (I) to shield drug from in vivo degradation; (II) to enhance drug availability by facilitating diffusion through endothelium; (III) to achieve a controlled and sustainable release over time; (IV) to improve intracellular penetration; (V) to impart or enhance particular capabilities thanks to surface modification. In literature several kinds of nanocarriers were studied in last decade (for ex., liposomes, nanogels, dendrimers, polymeric nanoparticles). In this topic, the present thesis focused on synthesis and characterization of self-assembling amphiphilic diblock copolymers for fabrication of nanoparticles (NPs). A deep characterization of NPs surface properties was done in collaboration with Department of Pharmacy, University of Naples Federico II. The biological properties of NPs were evaluated in collaboration with Department of Biology, University of Padova. Particular attention was given to the realization of well-defined block copolymers based on polycaprolactone (PCL) and polyethylene glycol (PEG) bearing functionalities able to improve or to impart specific properties to NPs (targeting, trafficking, antiangiogenic activity…). The first part of this work focused on new synthetic strategies to conjugate folic acid (Fol) and a peptide(aFLT1) to PEG end, in order to enhance surface exposure of Fol for active targeting and impart antiangiogenic properties to NPs. NPs properties and their biological activity were studied at first considering a single functionality, then combining together Fol and aFLT1. A new strategy to modify NPs surface morphology and enhance exposure of Fol was also developed It consists in giving a more extended conformation to the hydrophilic block by selectively threatening α-cyclodextrins onto PEG chains, realizing a supramolecular structure defined as polyrotaxane. The second part centers on synthesis and characterization of PCL end-terminated with amine groups, in order to tune NPs surface charge. Cationic NPs are, in fact, able to cross biological membranes enhancing uptake in cells, due to their strong interaction with negatively charged cell membranes. The last part deals with gene therapy. Small nucleic acids, as siRNA, can be absorbed onto positive charged NPs surface and delivered to the target site by multifunctional NPs. For this purpose, amphiphilic triblock copolymers possessing a second hydrophilic block bearing tertiary amines were synthetized. In order to fine tune the positive charge, and in this way the interaction with siRNA, a dimethylamino-ethyl methacrylate (DMAEMA) block was obtained through Atom Transfer Radical Polymerization (ATRP). This polymerization is well known to have as main advantage a fine control of molecular weight with low polydispersity.

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