0000000000397086
AUTHOR
Alessandro Donati
Hyaluronan Graft Copolymers Bearing Fatty-Acid Residues as Self-Assembling Nanoparticles for Olanzapine Delivery
In order to evaluate the potential of a technology platform based on hyaluronan copolymers grafted with propargylated ferulate fluorophores (HA-FA-Pg) in the development of drug delivery systems, the propargyl groups of HA-FA-Pg derivatives were employed with oleic acid (OA) or stearic acid (SA) residues across a biocompatible hexa(ethylene glycol) (HEG) spacer. The designed materials (i.e., HA-FA-HEG-OA or HA-FA-HEG-SA) showed clear-cut aggregation features in an aqueous environment, as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), generating nanoaggregate systems. In fact, HA-FA-HEG-OA and HA-FA-HEG-SA derivatives showed the property to create sel…
Polybenzofulvene derivatives bearing dynamic binding sites as potential anticancer drug delivery systems.
In order to obtain new advanced functional materials capable of recognizing drug molecules, the polybenzofulvene backbone of molecular brush poly-6-MOEG-9-TM-BF3k has been functionalized with a “synthetic dynamic receptor” composed of two 1-adamantylurea moieties linked together by means of a dipropyleneamino bridge as in Meijer's bis(adamantylurea) pincer (BAUP). This functional material, bearing synthetic receptors potentially capable of recognizing/loading and then delivering drug molecules, was used to prepare colloidal drug delivery systems (by means of soft interaction with BAUP) for delivering the model anti-cancer drug doxorubicin (DOXO). The resulting nanostructured drug delivery s…
Arsenic Pollution in the Southwest of Tuscany: Monitoring of Cornia Catchment Basin
The territory of Colline Metallifere, in SW Tuscany, is characterized by the presence of strong arsenic anomalies. Some hypotheses, formulated in the last 20 years, based on geological and mineralogical factors have failed to explain the peculiar distribution of this toxic element in soil, fluvial sediments and ground water. Our research group has been studying for four years the problem of arsenic pollution in this district to investigate the origin and the mechanism of As diffusion in the environment. In particular we started a comparative study based on the extensive sampling of the stream sediments of the main waterways of Colline Metallifere (Pecora, Bruna and Cornia and their tributar…
Design, Synthesis and Characterization of a Visible-Light-Sensitive Molecular Switch and Its PEGylation Towards a Self-Assembling Molecule.
HBDI-like chromophores represent a novel set of biomimetic switches mimicking the fluorophore of the green fluorescent protein that are currently studied with the hope to expand the molecular switch/motor toolbox. However, until now members capable of absorbing visible light in their neutral (i. e. non-anionic) form have not been reported. In this contribution we report the preparation of an HBDI-like chromophore based on a 3-phenylbenzofulvene scaffold capable of absorbing blue light and photoisomerizing on the picosecond timescale. More specifically, we show that double-bond photoisomerization occurs in both the E-to-Z and Z-to-E directions and that these can be controlled by irradiating …
Densely PEGylated polybenzofulvene brushes for potential applications in drug encapsulation
The technique of grafting side chains onto a linear polymeric backbone is commonly used to confer to the new polymeric material with desired properties, such as tunable solubility, ionic charge, biocompatibility, or specific interactions with biological systems. In this paper, two new polybenzofulvene backbones were assembled by spontaneous polymerization of the appropriate benzofulvene monomers (4,6-PO-BF3k and 4&rsquo
Nanoreactors for the multi-functionalization of poly-histidine fragments
Water-soluble MBHA derivatives were found to self-assemble in a water environment to generate aggregates showing core–shell architectures. The aggregates appeared to be capable of working as nanoreactors performing a multi-functionalization of poly-histidine fragments, which after an initial interaction with the solvated oligo(ethylene glycol) shell reach the reactive core.
Physicochemical Properties of A New PEGylated Polybenzofulvene Brush for Drug Encapsulation
A new polymer brush was synthesized by spontaneous polymerization of benzofulvene macromonomer 6-MOEG-9-T-BF3k bearing a nona(ethylene glycol) side chain linked to the 3-phenylindene scaffold by means of a triazole heterocycle. The polymer structure was studied by SEC-MALS, NMR spectroscopy, and MALDI-TOF MS techniques, and the results supported the role of oligomeric initiatory species in the spontaneous polymerization of polybenzofulvene derivatives. The aggregation features of high molecular weight poly-6-MOEG-9-T-BF3k-FE were investigated by pyrene fluorescence analysis, dynamic light scattering studies, and transmission electron microscopy, which suggested a tendency towards the format…
Hyaluronan-coated polybenzofulvene brushes as biomimetic materials
Hyaluronic acid (HA) forms pericellular coats in many cell types that are involved in the early stages of cell adhesion by interacting with the CD44 receptor. Based on the largely recognized overexpression of the CD44 receptor in tumor tissues, a polybenzofulvene molecular brush has been enveloped into hyaluronan shells to obtain a tri-component polymer brush (TCPB) composed of intrinsically fluorescent backbones bearing nona(ethylene glycol) arms terminated with low molecular weight HA macromolecules. The nanoaggregates obtained in TCPB water dispersions were characterized on the basis of dimensions, zeta potential, and in vitro cell toxicity. This biomimetic multifunctional material beari…
A Click Chemistry-Based “Grafting Through” Approach to the Synthesis of a Biorelevant Polymer Brush
A new biorelevant polymer brush showing a polybenzofulvene backbone was synthesized by a ‘‘grafting through’’ approach based on click chemistry and spontaneous polymerization reactions. The easy polymerization of the relatively complex monomer (6-MOEG-9-TM-BF3k) suggests the existence of a particularly efficient recognition process capable of pre-organizing the monomer molecules for the spontaneous polymerization. 13C-NMR spectroscopy as well as UV-vis and fluorescence spectroscopy suggested for poly-6-MOEG-9-TM-BF3k the features of a vinyl (1,2) p-stacked polymer. The new polybenzofulvene derivative was found to interact with water at room temperature to give clear water solutions, but TEM…
Hyaluronan-Based Graft Copolymers Bearing Aggregation-Induced Emission Flurogens
In order to develop a technology platform based on two natural compounds from biorenewable resources, a short series of hyaluronan (HA) copolymers grafted with propargylated ferulic acid (HA-FA-Pg) were designed and synthesized to show different grafting degree values and their optical properties were characterized in comparison with reference compounds containing the same ferulate fluorophore. Interestingly, these studies revealed that the ferulate fluorophore was quite sensitive to the restriction of intramolecular motion and its introduction into the rigid HA backbone, as in HA-FA-Pg graft copolymers, led to higher photoluminescence quantum yield values than those obtained with the isola…
Combining Spontaneous Polymerization and Click Reactions for the Synthesis of Polymer Brushes: A "Grafting Onto" Approach
Two novel benzofulvene monomers bearing propargyl or allyl groups have been synthesized by means of readily accessible reactions, and were found to polymerize spontaneously by solvent removal, in the apparent absence of catalysts or initiators, to give the corresponding polybenzofulvene derivatives bearing clickable propargyl or allyl moieties. The clickable propargyl and allyl groups were exploited in appropriate click reactions to develop a powerful and versatile "grafting onto" synthetic methodology for obtaining tailored polymer brushes.