Recent advances in nanotechnology are greatly encouraging the design of new sophisticated biomaterials-based platforms, owing a series of peculiar characteristics and with increasingly complex functions. Such fine materials are often designed to mimic a subset of the physicochemical properties of natural materials. Knowledge gained from fundamental studies is being used in conjunction with fabrication methods such as self-assembly to design biomaterials that optimally interface with the biology of the host. This thesis focuses the attention on the development of new biomaterials based on cationic poly-cyclodextrin (PolyCD) and hyaluronic acids (HA). Physicochemical properties of such engineered platforms were tailored by chemical modification using covalent and/or not covalent approaches. Complementary techniques including UV/Vis, steady-state, time-resolved fluorescence, DLS, zeta potential measurements, 1H and 13C NMR, Maldi-TOF etc. have been employed for the characterization of the functionalized polymers. Figure 1 reports a general overview of different nanodevices developed during PhD research activity. These engineered systems have revealed a broad versatility for their potential biological applications and have been investigated as carriers for drug delivery, hydrogel components and biosensing materials. The thesis is structured in four chapters. Chapter I reports an overview of the main characteristics of hyaluronic acid derivatives and cyclodextrin polymers: selected examples of literature data summarize the main biological applications describing the currently available procedures for their functionalization. Chapter II deals about the nanoassemblies based on PolyCD loaded with the non-steroidal anti-inflammatory drug Diclofenac (DCF) and linked by supramolecular interactions with a fluorescent probe (adamantanyl-Rhodamine conjugate, Ada-Rhod). PolyCD-based nanoassemblies were investigated as anti-inflammatory nanomedicines to tackle critical pathological inflammation in osteoarticular diseases. Chapter III reports the synthesis of new hyaluronic acid derivatives obtained by conjugation and click chemistry reactions. HA derivatives have been investigated as hydrogel components and as platforms for the delivery of antiviral drugs. Specifically, this section reports the results of the research project about supramolecular hydrogels obtained during an abroad research period carried out at the Institute of Soft Nanoscience of the Westfälische Universität in Münster (Germany), under the supervision of Prof. Bart Jan Ravoo. Finally, Chapter IV describes the preliminary results about the synthesis and characterization of Gold@Silver Core-Shell nanoparticles (Au@Ag NPs), coated by a polymeric matrix. Specifically, the synthesis, the physicochemical properties and the interaction with selected Raman reporters (RaRs) of Gold@Silver Core-Shell NPs obtained from cationic poly-cyclodextrin (PolyCD), Hyaluronic Acid (HA), and Hyaluronic acid modified with β-cyclodextrins (HA-CD) will be discussed. Gold@Silver NPs are proposed as SERS-Tag for exosomes recognition. Exosomes are a subgroup of cell-derived nanosized extracellular vesicles that have been recently recognized as new mediators for many cellular processes. They emerged as potential biomarkers for non-invasive disease diagnosis and monitoring of treatment response, especially in cancer therapy. This research project is carried out in collaboration with Prof. Simion Astilean and Dr. Alexandru Hada from the Interdisciplinary Research Institute in BioNano-Sciences, Babes-Bolyai University (Romania).
|Titolo:||Engineered biomaterials based on Hyaluronic Acid and Cyclodextrin supramolecular assemblies for therapy and diagnosis|
|Data di pubblicazione:||11-dic-2020|
|Appare nelle tipologie:||Tesi di dottorato|