Endocytosis of emerging nanomedicines: Understanding the influence of shape of 3D nanoprinted soft matter materials

点击翻译按钮获取中文摘要

REMIT: This "Basic Bioscience" project addresses BBSRC's strategic research priority 3, "Bioscience for Health" as it aims to develop basic bioscience underpinning the formulation and effectiveness of emerging nanomedicines that will benefit the maintenance and promotion of health.THE PROBLEM:Little is known how the interdependency of size, shape, and surface chemistry can influence the biodistribution, cellular internalization, and intracellular trafficking of nanomaterials. Insights into the effect of shape, patterning, and deformability on cellular uptake and biodistribution are emerging with the increase in sophisticated techniques to manufacture nanomedicines such as 3D nanoprinting that can generate monodisperse products of specific geometry and deformability. Patterning on surfaces can also influence protein adsorption and consequently cellular responses.CONTEXT:With the first regulatory approved 3D printed medicine in 2015, the precendence was set for the use of 3D printing in the pharmaceutical industry and interest in exploring capabilities in the nanoscale (I.e. 3D nanoprinting) is rapidly increasing. One of the attractive advantages of 3D printing its versatility and diversity which can be exploited in the health sector to develop personalised medicines. 3D nanoprinting in healthcare extends capabilities and potential into the relm of nanomedicines.Nanomedicines can employ multiple pathways for cellular entry, which are currently insufficiently understood.Various mechanisms of endocytosis are available to nanomedicines including phagocytosis and pinocytosis through clathrin-dependent and clathrin-independent pathways.PROJECT AIMS:This project will explore to process of endocytosis of 3D nanoprinted soft matter materials and investigate the shape effect of these nanomaterials on cellular internalization, and intracellular trafficking.PhD WORK PROGRAMME:Key resources to be used:- Nikon Imaging Centre: The world renowed Nikon Imaging Centre was established in 2012 at King's College London. As one of only 8 Nikon Imaging Centres in the world and the only one in the UK, the £4.5 million centre houses ten different cutting-edge research microscopes. This project will involve imaging the dynamics of endocytosis in animal and plant cell lines using cutting edge research microscopic techniques such as the Ti2 live cell imaging systems available at the Nikon Imaging centre.- London Centre for Nanotechnology (LCN): LCN is a multidisciplinary research centre in physical and biomedical nanotechnology in London. King's College London recently joined the LCN and Dr Raimi- Abraham has an ongoing collaboration with Dr Richard Thorogate (BioNano Laboratory) in the area of quantitative nanomechanical characterisation of soft matter nanomaterials. The project will explore the assessment of morphological changes of plasma membrane and protein assembly during endocytosis utilizing high-speed atomic force microscopy (HS-AFM) combined with concofocal laser scanning unit.YEAR ONE (KCL):- Student training in project relevant techniques such as 3D nanoprinting, cell culture, high resolution electron microscopy (for imaging of cells and their interaction with 3D nanoprinted soft matter materials), intra-vtiral microscopy, atomic force microscpy and confocal microscopy).ii) Fabricate templates for 3D nanoprinting.YEAR TWO (KCL & BASF):- Formulation of 3D nanofeatures with various shapes- Characterisation of surface properties such as roughness and understanding of potential interaction with the cells for uptake.YEAR THREE (KCL):- Analyze the effects of nanopatterns on the biological function of living animal (such as Caco-2 cell line or TR146 cell line) and plant cells (such as Tobacco BY-2 cells)YEAR FOUR (KCL & BASF):- Feedback the results of biological studies to redefine and generate new knowledge based on cell- material interactions at nanometre scales.