The self-assembly of lipids into organized soft matter is ubiquitous in natural systems. The most prominent example is the lamellar structural unit of cell membranes, though the occurrence of several non-lamellar assemblies – such as cubic and hexagonal mesophases – is currently emerging as crucially connected to particular functions or pathological conditions. On the synthetic side, a wide range of lipid architectures can be built from amphiphilic lipids, and their structure can be controlled by varying the experimental conditions – such as temperature, pressure, pH, ionic strength and geometrical local constraints – in order to reproduce the same morphologies, found in living systems. These synthetic assemblies represent simplified mimics of the aforementioned biological interfaces. Furthermore, their biocompatibility – combined with the coexistence of hydrophobic and hydrophilic domains with morphology and spatial organization ruled by thermal equilibrium – lends itself to applications in the biomedical field, e.g. for the delivery of therapeutic or diagnostic active principles. In this research work, the attention has been focused on the investigation of the effects of inorganic nanoparticles and molecular additives on the phase properties of lipid liquid-crystalline mesophases. In particular, the inclusion of gold (AuNPs) and iron oxide (SPIONs) nanoparticles coated with hydrophobic ligands in liquid crystalline mesophases has been explored to build up smart soft hybrid materials, where the biocompatibility of the lipid matrix (1-monoolein and phytantriol) mesophases is combined with the responsiveness to external stimuli, provided by the NPs. For cubic mesophases doped with hydrophobic AuNPs and SPIONs, the effects of NPs inclusion – both on the arrangement of the mesophase and on its rheological properties – have been investigated. For lipid cubic phases doped with SPIONs, we examined the magnetic properties and their dependence on the phase state and monitored in-situ the structural change caused by an oscillating magnetic field. To further modulate the phase behavior, and to tailor the size of hydrophobic and hydrophilic compartments, we studied the effects of additives with different polarities – i.e. sugar esters, oils (tetradecane) and other lipids (DOPG) – on the lattice parameters and stability of mesophases. To gain additional insight on the confinement of molecular and macromolecular active principles, we monitored the diffusion of hydrophilic probes of different sizes through fluorescence correlation spectroscopy and the results have been interpreted in terms of motion dimensionality and size match between the probes and the hydrophilic channels. In addition, the enzymatic activity of a model enzyme – the alkaline phosphatase – has been investigated when the enzyme or the probe were included in the mesophase. Finally, in-vitro tests on tumor cell lines provided information on biocompatibility and internalization, highlighting the potential of these hybrid systems as drug-delivery devices.

Effects of inorganic nanoparticles and additives on the properties of lipid liquid crystalline mesophases / Marco Mendozza; Debora Berti. - (2020).

Effects of inorganic nanoparticles and additives on the properties of lipid liquid crystalline mesophases

Marco Mendozza
Writing – Original Draft Preparation
;
Debora Berti
Supervision
2020

Abstract

The self-assembly of lipids into organized soft matter is ubiquitous in natural systems. The most prominent example is the lamellar structural unit of cell membranes, though the occurrence of several non-lamellar assemblies – such as cubic and hexagonal mesophases – is currently emerging as crucially connected to particular functions or pathological conditions. On the synthetic side, a wide range of lipid architectures can be built from amphiphilic lipids, and their structure can be controlled by varying the experimental conditions – such as temperature, pressure, pH, ionic strength and geometrical local constraints – in order to reproduce the same morphologies, found in living systems. These synthetic assemblies represent simplified mimics of the aforementioned biological interfaces. Furthermore, their biocompatibility – combined with the coexistence of hydrophobic and hydrophilic domains with morphology and spatial organization ruled by thermal equilibrium – lends itself to applications in the biomedical field, e.g. for the delivery of therapeutic or diagnostic active principles. In this research work, the attention has been focused on the investigation of the effects of inorganic nanoparticles and molecular additives on the phase properties of lipid liquid-crystalline mesophases. In particular, the inclusion of gold (AuNPs) and iron oxide (SPIONs) nanoparticles coated with hydrophobic ligands in liquid crystalline mesophases has been explored to build up smart soft hybrid materials, where the biocompatibility of the lipid matrix (1-monoolein and phytantriol) mesophases is combined with the responsiveness to external stimuli, provided by the NPs. For cubic mesophases doped with hydrophobic AuNPs and SPIONs, the effects of NPs inclusion – both on the arrangement of the mesophase and on its rheological properties – have been investigated. For lipid cubic phases doped with SPIONs, we examined the magnetic properties and their dependence on the phase state and monitored in-situ the structural change caused by an oscillating magnetic field. To further modulate the phase behavior, and to tailor the size of hydrophobic and hydrophilic compartments, we studied the effects of additives with different polarities – i.e. sugar esters, oils (tetradecane) and other lipids (DOPG) – on the lattice parameters and stability of mesophases. To gain additional insight on the confinement of molecular and macromolecular active principles, we monitored the diffusion of hydrophilic probes of different sizes through fluorescence correlation spectroscopy and the results have been interpreted in terms of motion dimensionality and size match between the probes and the hydrophilic channels. In addition, the enzymatic activity of a model enzyme – the alkaline phosphatase – has been investigated when the enzyme or the probe were included in the mesophase. Finally, in-vitro tests on tumor cell lines provided information on biocompatibility and internalization, highlighting the potential of these hybrid systems as drug-delivery devices.
Debora Berti
ITALIA
Marco Mendozza; Debora Berti
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/1226755
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