Periodic Reporting for period 1 - NanoFusion (Effect of nanoparticles on membrane fusion)
Periodo di rendicontazione: 2022-06-01 al 2024-05-31
Artificial nanomaterials have become the focus of intense research in the field nanomedicine because they possess novel functionalities, stabilities and tunability. In particular, nanoparticles (NPs) of different sizes, shapes, materials, and surface chemistry are widely studied as functional components for applications such as medical imaging, theragnostic, targeted therapy, drug delivery and biosensing. Considering its crucial importance to the design and use of nanomaterials in many biomedical applications where nanotoxicity should be minimized, there is an urgent need for a better fundamental understanding of the interactions between functional NPs and model cell membranes. In recent years, nano-ions (charged nanoparticles) have attracted increasing interest due to their fascinating properties. Nano-ions such as polyoxometalates (POMs), boron clusters and hydrophobic ions, are nanometric well-defined molecular metal clusters with variety of structures – of different size, shape, and charge, which depend on the atomic composition. This enables precise control of their biological activity at the cell membrane interface. Nano-ions have promising antitumor, anti-infectious and anti-Alzheimer’s activities. Despite their promising membrane-targeting ability, direct evidence for the proposed mechanism based on the formation and desorption of POM-lipid assemblies is lacking. Their interactions with cell membranes, relevant to their cytotoxicity and drug delivery applications, remain poorly understood. In particular, little is known how the presence of nano-ions might influence the formation, reorganization and evolution of the structure and morphology of SLBs. The overall objective of this project was to understand the effect of NPs on membrane fusion.
As model nanoparticles, the nano-ions (Keggin-type POM and hydrophobic ions) were used. A systematic study of the formation of supported lipid bilayers (SLBs) with adsorbed and/or invading nano-ions was conducted, investigating the process for liposome surface fusion mediated by nano-ions. The SLBs with and/or without nano-ions at the solid-air and solid-liquid interfaces have been evaluated and correlated with their self-assembled structure in the solution. The mechanism for the nano-ion SLB formation process, kinetics, and structural evolution via liposome fusion route has been developed. The structural and morphological changes of SLBs upon interactions with nano-ions have been fully characterised. The results has generated unprecedented insights into how the physicochemical properties of nano-ions influence the liposome structure.
In addition, the structural changes and molecule packing of lipid monolayer on subphase with various nano-ions have been investigated. These unprecedented results has offered insights into fundamental interactions between nano-ions and model cell membranes, underpinning/demonstrating the potential of nano-ions for use as novel membrane targeting bioactive nanomedicine with well-defined and controllable structure and activities.
In addition, the structural changes and molecule packing of lipid monolayer on subphase with various nano-ions have been investigated. These unprecedented results has offered insights into fundamental interactions between nano-ions and model cell membranes, underpinning/demonstrating the potential of nano-ions for use as novel membrane targeting bioactive nanomedicine with well-defined and controllable structure and activities.
The fundamental insights of nano-ions mediated membrane fusion gained from this project, relevant to our understanding interactions between model membranes (liposomes, SLBs and lipid monolayer) and nano-ions goes beyond the state-of-the-art. The formation, reorganization and evolution of the structure and morphology of nano-ions laden SLBs has not been previously reported. The molecular architecture of liposomes with nano-ions has been evaluated for the first time, demonstrating their promising potential in medical applications.
The results have been widely disseminated to academic audience through a variety of mechanisms, including seminars, group meetings, invited talks at other institutes, conference presentations. Two manuscripts are under preparation. The fellow has also interacted synergistically with the host group, learning and developing new experimental and scientific skills.
The results have been widely disseminated to academic audience through a variety of mechanisms, including seminars, group meetings, invited talks at other institutes, conference presentations. Two manuscripts are under preparation. The fellow has also interacted synergistically with the host group, learning and developing new experimental and scientific skills.