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The utilisation of cell-membrane wrapped nanoparticles as a novel CNS drug delivery system


   Faculty of Health and Life Sciences

  Dr Susan Hawthorne, Dr Bridgeen Callan  Monday, February 27, 2023  Competition Funded PhD Project (Students Worldwide)

About the Project

Cell membrane-wrapped nanoparticles (NP) are under investigation in multiple applications from vaccines to drug delivery systems due to their prolonged circulation time, reduced uptake by the mononuclear phago-cyte system, as well as tissue- and inflammation-targeting properties. Once injected in a physiological environment, NP interact with biological components and are surrounded by a protein corona (PC). The PC, the set of proteins binding to the NP surface, plays a critical role in particle recognition by the innate immune system and can affect NP toxicity and targeting capabilities.

To address these issues, current research has focused on mimicking nature using cells for the design of bioinspired nanocarriers, in particular cell membranes. The so-called cell-membrane wrapped NP are composed of a synthetic NP surrounded by a layer of natural cell membrane. This cell membrane coating technology allows the design of biomimetic nanocarriers, whose surfaces replicate the complex properties of the source cells from which their membranes are derived.  We have developed a polymer-based nanoparticlulate drug delivery system which can specifically target the blood brain barrier (BBB) delivering encapsulated therapeutics across this biological hurdle.

The aim of this project is to optimise this drug delivery system using cell membrane wrapping technology, to reduce the formation of PC and increase stability and targeting capabilities of our drug delivery system in physiological environments.

Please note: Applications for more than one PhD studentship are welcome, however if you apply for more than one PhD project within Biomedical Sciences, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission. If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a PhD studentship. In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.


References

Recommended reading:
Fontana et al. (2020) Influence of Cell Membrane Wrapping on the Cell−Porous Silicon Nanoparticle Interactions. Adv.Healthcare Mat. DOI: 10.1002/adhm.202000529
Han et al. (2021) Macrophage membrane-coated nanocarriers co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice. Bioactive Materials https://doi.org/10.1016/j.bioactmat.2020.08.017
Huey et al. (2017) Targeted drug delivery system to neural cells utilizes the nicotinic acetylcholine receptor. Int. J.Pharmaceutics doi.org/10.1016/j.ijpharm.2017.04.023
Huey et al. (2019) Design, stability and efficacy of a new targeting peptide for nanoparticulate drug delivery to SH-SY5Y neuroblastoma cells. J. Drug Targeting doi:10.1080/1061186X.2019.1567737
Singh et al. (2021) In vivo protein corona on nanoparticles: does the control of all material parameters orient the biological behavior? Nanoscale Adv. DOI: 10.1039/d0na00863j
Zhang et al. (2021) Neural Cell Membrane-Coated Nanoparticles for Targeted and Enhanced Uptake by Central Nervous System Cells. Applied Mat. Interfaces https://doi.org/10.1021/acsami.1c16543
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