Smeraldo, Alessio (2021) Biopolymer nanostructures for precision imaging: basic principles and applications to nanomedicine. [Tesi di dottorato]

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Item Type:	Tesi di dottorato
Resource language:	English
Title:	Biopolymer nanostructures for precision imaging: basic principles and applications to nanomedicine
Creators:	Creators Email Smeraldo, Alessio alessio.smeraldo@unina.it
Date:	13 December 2021
Number of Pages:	109
Institution:	Università degli Studi di Napoli Federico II
Department:	Ingegneria Chimica, dei Materiali e della Produzione Industrialea
Dottorato:	Ingegneria dei prodotti e dei processi industriali
Ciclo di dottorato:	34
Coordinatore del Corso di dottorato:	nome email D'Anna, Andrea anddanna@unina.it
Tutor:	nome email Torino, Enza UNSPECIFIED
Date:	13 December 2021
Number of Pages:	109
Keywords:	precision imaging; microfluidics; artificial neural networks
Settori scientifico-disciplinari del MIUR:	Area 09 - Ingegneria industriale e dell'informazione > ING-IND/34 - Bioingegneria industriale
Date Deposited:	05 Jan 2022 07:13
Last Modified:	28 Feb 2024 11:43
URI:	http://www.fedoa.unina.it/id/eprint/14289

Collection description

Nowadays, CT and MR are the most widespread imaging modalities thanks to their ability to provide important anatomical information that are essential to achieve a reliable and accurate diagnosis. Despite the differences in their operating principles, each one with its own pros and cons, both techniques often require the injection of contrast agents (CAs) in order to make visible anatomical details otherwise not appreciable. Elements with high atomic number are used in CT to increase X-rays attenuation in the region of interest while, for MRI, paramagnetic atoms are chosen to act on the characteristic relaxation times of each tissue. Despite their extensive use, several drawbacks about the in vivo behavior of CAs have been recently highlighted. In fact, although different ligands are used to improve their performances and in vivo stability, CAs suffer from some limitations such as absence of specificity toward the target site, a rapid clearance from the bloodstream that allows short acquisition times and high toxicity due to their in vivo dissociation and deposition in organs such as brain, thyroid, and kidneys. For this reason, a particular attention has been recently drawn to molecular imaging, interpreted as the characterization of biological and physiological processes at the cellular and/or molecular level. In addition to the possibility to drastically reduce the CAs dose, this methodology allows a dynamic and noninvasive monitoring of various diseases, before their clear macroscopic manifestation, leading to an early diagnosis. To achieve this goal, a contrast agent with high sensitivity and specificity to target a specific tissue or cell type is required for successful imaging. Moreover, this higher selectivity allows the combined use of more CAs heading toward the increasing use of multimodal imaging modalities such as PET/MRI and PET/CT that are able to provide anatomical details and functional information simultaneously. Among all the possible probes, nanoparticles are emerging as a powerful tool for molecular and multimodal imaging thanks to their small size, their easily functionalizable surface and their ability to encapsulate more than one agent. In addition, through a suitable choice of the materials, it is possible to improve CAs biocompatibility but in particular influence their performances acting on the fundament parameters that leads to the generation of the imaging signal. For example, the presence of a hydrophilic polymer matrix around a gadolinium-based CAs allows to attract a large amount of water and increases the interactions between water molecules and the metal chelate promoting a relaxivity boosting. The effect, described by the Hydrodenticity concept, can be modulated through a proper control of the structural properties of polymer-based nanohydrogels affects the water molecules' dynamics resulting at specific condition in a relaxivity boost. The present PhD work aims to build up innovative CAs, for both the single and multimodal imaging modalities, able to provide diagnostic information at molecular level through the use of biopolymeric nanocarriers. In particular starting by a detailed study of the interaction mechanisms between CAs and polymeric matrix and how this latter influences the CAs performances, the goal is to finely tune the nanostructures properties thanks to a microfluidic approach in order to improve the performances of clinically used CAs increasing their specificity and sensitivity towards the molecular target.

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