Rational engineering of Apoferritin-based nanoparticles for drug delivery

Effective drug delivery remains a major challenge in treating diseases like cancer, where targeted delivery systems are critical for maximizing efficacy and minimizing side effects. Drug delivery systems (DDS) offer a promising solution, and apoferritin, a protein-based nanoparticle, has shown consi...

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Main Author: Crowhurst, Samuel
Format: Thesis (University of Nottingham only)
Language:English
Published: 2025
Subjects:
Online Access:https://eprints.nottingham.ac.uk/80968/
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author Crowhurst, Samuel
author_facet Crowhurst, Samuel
author_sort Crowhurst, Samuel
building Nottingham Research Data Repository
collection Online Access
description Effective drug delivery remains a major challenge in treating diseases like cancer, where targeted delivery systems are critical for maximizing efficacy and minimizing side effects. Drug delivery systems (DDS) offer a promising solution, and apoferritin, a protein-based nanoparticle, has shown considerable potential as a DDS due to its biocompatibility and capacity for drug encapsulation. However, the effectiveness of apoferritin for drug delivery is limited by the leakage of small drug molecules through its surface pores, which prevents drug accumulation at a target site. Addressing this challenge through the structural engineering of apoferritin’s pores could expand its utility, enabling it to encapsulate a wider range of therapeutic agents. This thesis aims to provide directives for potential pore modifications to optimise ferritin as a versatile nanocarrier capable of retaining even small, leakage-prone drugs. This is achieved through the use of in silico molecular dynamics simulations to minimise small molecule drug leakage by mutating the ferritin threefold and fourfold surface pores. The analysis of these modifications is supported by a streamlined protocol for the in silico analysis of mutants focusing on their structural stability and ability to minimise pore leakage. Preliminary experimental work is provided from which future work can validate these results in vitro.
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spelling nottingham-809682025-07-30T04:40:14Z https://eprints.nottingham.ac.uk/80968/ Rational engineering of Apoferritin-based nanoparticles for drug delivery Crowhurst, Samuel Effective drug delivery remains a major challenge in treating diseases like cancer, where targeted delivery systems are critical for maximizing efficacy and minimizing side effects. Drug delivery systems (DDS) offer a promising solution, and apoferritin, a protein-based nanoparticle, has shown considerable potential as a DDS due to its biocompatibility and capacity for drug encapsulation. However, the effectiveness of apoferritin for drug delivery is limited by the leakage of small drug molecules through its surface pores, which prevents drug accumulation at a target site. Addressing this challenge through the structural engineering of apoferritin’s pores could expand its utility, enabling it to encapsulate a wider range of therapeutic agents. This thesis aims to provide directives for potential pore modifications to optimise ferritin as a versatile nanocarrier capable of retaining even small, leakage-prone drugs. This is achieved through the use of in silico molecular dynamics simulations to minimise small molecule drug leakage by mutating the ferritin threefold and fourfold surface pores. The analysis of these modifications is supported by a streamlined protocol for the in silico analysis of mutants focusing on their structural stability and ability to minimise pore leakage. Preliminary experimental work is provided from which future work can validate these results in vitro. 2025-07-30 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/80968/1/Samuel%20Crowhurst%20-%20Thesis_Corrections_Final.pdf Crowhurst, Samuel (2025) Rational engineering of Apoferritin-based nanoparticles for drug delivery. MRes thesis, University of Nottingham. nanoparticles Apoferritin drug delivery
spellingShingle nanoparticles
Apoferritin
drug delivery
Crowhurst, Samuel
Rational engineering of Apoferritin-based nanoparticles for drug delivery
title Rational engineering of Apoferritin-based nanoparticles for drug delivery
title_full Rational engineering of Apoferritin-based nanoparticles for drug delivery
title_fullStr Rational engineering of Apoferritin-based nanoparticles for drug delivery
title_full_unstemmed Rational engineering of Apoferritin-based nanoparticles for drug delivery
title_short Rational engineering of Apoferritin-based nanoparticles for drug delivery
title_sort rational engineering of apoferritin-based nanoparticles for drug delivery
topic nanoparticles
Apoferritin
drug delivery
url https://eprints.nottingham.ac.uk/80968/