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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Research Repository ...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Research Repository UCD
Doctoral thesis . 2025
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Time-resolved recovery of intracellular magnetic nanoparticles

Authors: Sheridan, Emily;

Time-resolved recovery of intracellular magnetic nanoparticles

Abstract

Engineered nanomaterials and their applications are already with us in consumer products, electronics and in the biomedical industry. Recent clinical translation of novel nanotherapeutics highlight the potential of nanotechnology to change the clinical landscape and the gains that are continuing to be made. The longstanding goal of nanomedicine is towards the development of precision medicines, and multimodal agents for diagnostics and therapeutic agents. Inorganic nanomaterials provide unique advantages in achieving these goals, but their clinical translation has been slower than for their organic counterparts. The major barrier to their success is in their long term biocompatibility, biodistribution, and intracellular degradation which events their ability to deliver therapeutic cargo. Designing effective nanotherapeutics has looked to biocompatible nanomaterials coupled with passive or active targeting to reach their target site in the body and has been the focus of much research. Overcoming the barriers to biodistribution however the nanoparticle then encounters the intracellular machinery which adds a whole new layer of complexity. Designing nanotherapeutics to effectively avoid degradation inside the cell while delivering their therapeutic cargo requires a deeper understanding of the intracellular processing of nanomaterials by the cell machinery. In this work, the time-resolved intracellular trafficking of nanoparticles was studied. Using magnetic nanoparticles to recovery nanoparticles as they move through the endosomal pathway, the nanoparticles populations could be recovered shortly after uptake at the cellular membrane contained in early endosomes and over time move into lysosomes. The rapid recovery of nanoparticle-containing vesicles was optimized to yield intact and functionally active vesicles which were provided snapshots of the evolving microenvironment of the nanoparticle inside the cell. This protocol could be reproduced across cell and corona types presenting a valuable method for future studies of intracellular nanoparticle trafficking. Recovery of early nanoparticle trafficking events in the early endocytic machinery provided hints to nanoparticle uptake routes into the cell and how the contacts between intracellular organelles developed over time. Proteomics also revealed the unexpected presence of RNA machinery related proteins associated with early vesicles which was investigated further. The extraction of RNA from the early vesicles allowed presented new ideas of how RNA-machinery could potentially be linked to the endosomal pathway and time-resolved nanoparticle recovery and mRNA sequencing revealed time-dependent evolution of the local RNA at the sites of nanoparticle trafficking. This work demonstrates the ability of the magnetic nanoparticle recovery to reveal more insights into the nature of nanoparticle trafficking with implications in potential mechanisms governing the intracellular sorting, sensing, or regulation of nanoparticle trafficking.

Country
Ireland
Related Organizations
Keywords

Magnetic, Endosome, Nanoparticles, Bionanoscience

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
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