Despite the potentially revolutionary impact of the use of nanomaterials in medical applications, the number of nanoparticles (NPs) approved for clinical trials is still very limited. This limitation is also attributed to a lack of fundamental knowledge on the biological fate of NPs once introduced in the complex and heterogenous environment of living systems. To fill this gap, a vast research area focuses on disentangling the intricate nature of the nano-bio interface, i.e., the interface between NPs and biological systems, to predict the NPs' biological impact and potential cytotoxicity. With this purpose, synthetic lipid membranes rapidly emerged as biomimics to study the nanobio interface in simplified and controlled conditions, providing a simplistic yet comprehensive understanding of membrane-related phenomena. In this field, recent reports showed that citrate-capped gold nanoparticles (AuNPs) spontaneously aggregate on synthetic zwitterionic membranes with a membranetemplated process dependent on the rigidity of the membranes and the surface functionalization of the inorganic NPs. Despite the potential relevance of this peculiar aggregative phenomenon, its mechanistic and kinetic aspects were not completely understood. In the present thesis, the interaction between citrated inorganic nanoparticles and synthetic and natural membranes was thoroughly investigated, aiming at: i) contributing to improving the fundamental knowledge on the nano-bio interface; ii) designing straightforward approaches for the synthesis of novel engineered hybrid nanomaterials; iii) demonstrating that the NPs-membrane interaction can be exploited for the characterization of free-standing vesicles and inorganic NPs-vesicles hybrids. Accordingly, the first section of this work focuses on unveiling the roles of viscoelastic properties of bilayers as well as the chemical nature of the particles in the membranetemplated aggregative phenomenon. Then, in the second section we demonstrate that the plasmonic properties of AuNPs can be conveniently exploited as nanoprobes for determining the stiffness of synthetic and natural vesicles and estimating the extent of lipid coverage of membrane-camouflaged NPs for targeted nanomedical applications. Finally, the last part of the work shows that magneto-plasmonic citrated NPs can be easily combined with liposomes through spontaneous self-assembly to produce multifunctional materials which combine the properties of inorganic particles with the biocompatibility of lipid scaffolds. In conclusion, the results presented in this work provide an overall description of the association of citrated NPs with lipid structures, shedding light on the main energetic contributions that drive the interaction and demonstrating its technological relevance, paving the way for the development of novel strategies for the production and characterization of nanomaterials.

THE NANO-BIO INTERFACE AS A PLATFORM FOR TECHNOLOGICAL APPLICATIONS / Jacopo Cardellini. - (2023).

THE NANO-BIO INTERFACE AS A PLATFORM FOR TECHNOLOGICAL APPLICATIONS

Jacopo Cardellini
2023

Abstract

Despite the potentially revolutionary impact of the use of nanomaterials in medical applications, the number of nanoparticles (NPs) approved for clinical trials is still very limited. This limitation is also attributed to a lack of fundamental knowledge on the biological fate of NPs once introduced in the complex and heterogenous environment of living systems. To fill this gap, a vast research area focuses on disentangling the intricate nature of the nano-bio interface, i.e., the interface between NPs and biological systems, to predict the NPs' biological impact and potential cytotoxicity. With this purpose, synthetic lipid membranes rapidly emerged as biomimics to study the nanobio interface in simplified and controlled conditions, providing a simplistic yet comprehensive understanding of membrane-related phenomena. In this field, recent reports showed that citrate-capped gold nanoparticles (AuNPs) spontaneously aggregate on synthetic zwitterionic membranes with a membranetemplated process dependent on the rigidity of the membranes and the surface functionalization of the inorganic NPs. Despite the potential relevance of this peculiar aggregative phenomenon, its mechanistic and kinetic aspects were not completely understood. In the present thesis, the interaction between citrated inorganic nanoparticles and synthetic and natural membranes was thoroughly investigated, aiming at: i) contributing to improving the fundamental knowledge on the nano-bio interface; ii) designing straightforward approaches for the synthesis of novel engineered hybrid nanomaterials; iii) demonstrating that the NPs-membrane interaction can be exploited for the characterization of free-standing vesicles and inorganic NPs-vesicles hybrids. Accordingly, the first section of this work focuses on unveiling the roles of viscoelastic properties of bilayers as well as the chemical nature of the particles in the membranetemplated aggregative phenomenon. Then, in the second section we demonstrate that the plasmonic properties of AuNPs can be conveniently exploited as nanoprobes for determining the stiffness of synthetic and natural vesicles and estimating the extent of lipid coverage of membrane-camouflaged NPs for targeted nanomedical applications. Finally, the last part of the work shows that magneto-plasmonic citrated NPs can be easily combined with liposomes through spontaneous self-assembly to produce multifunctional materials which combine the properties of inorganic particles with the biocompatibility of lipid scaffolds. In conclusion, the results presented in this work provide an overall description of the association of citrated NPs with lipid structures, shedding light on the main energetic contributions that drive the interaction and demonstrating its technological relevance, paving the way for the development of novel strategies for the production and characterization of nanomaterials.
2023
Debora Berti
ITALIA
Jacopo Cardellini
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1302706
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