Multifunctional polyester-based stimuli-responsive polymeric nanoparticles for therapeutic delivery
File(s)
Author(s)
Lu, Xinyu
Type
Thesis
Abstract
The work presented in this thesis focuses on addressing the challenges associated with the effective delivery of therapeutic agents, particularly biomacromolecules like nucleic acids. The fragility of these biomacromolecules, coupled with low cellular uptake and inadequate endosomal escape, poses significant hurdles to achieving optimal therapeutic efficacy. This thesis presents the work involving the development of multifunctional polyesters and multifunctional polyester-based stimuli-responsive polymeric nanoparticles for enhanced drug delivery and improved thermostability.
The quantitative one-pot iterative living ring-opening polymerisation (QOIL-ROP) method previously developed for the synthesis of sequence-controlled multifunctional polyesters has been improved, enabling the synthesis of sequence-controlled polyesters with improved biocompatibility and enhanced functionality.
The self-assembly of multifunctional polyesters in the aqueous environment was investigated. The effects of polyester chemical structure and the adopted self-assembly approach on the self-assembly of multifunctional polyesters were examined.
A novel self-amplifying RNA (saRNA) delivery platform based on cationic PEGylated polyesters has been developed. The effects of amine position in a polyester chain on saRNA delivery were studied. The effects of positive charge density and molecular weight of the polyester on saRNA delivery were further investigated. The long-term thermostability of the optimal saRNA-loaded polymeric nanoparticles was evaluated.
A series of sequence-controlled multifunctional polyesters with different molecular wights and block sequences were designed and synthesised for effective saRNA delivery. The effects of polyester molecular weight and block sequence on self-assembly and cell transfection were investigated. The long-term thermostability of the optimal micelleplexes was assessed.
A series of sequence-controlled multifunctional polyesters were employed for intestinal drug delivery via oral administration. Due to the unique pH-responsiveness of the polyesters, drugs were retained within the self-assembled polymeric nanoparticles in acidic aqueous environments like gastric fluids, but were partially released in relatively neutral or basic aqueous solutions like intestinal fluids. The long-term colloidal stability of the polymeric nanoparticles was investigated.
The quantitative one-pot iterative living ring-opening polymerisation (QOIL-ROP) method previously developed for the synthesis of sequence-controlled multifunctional polyesters has been improved, enabling the synthesis of sequence-controlled polyesters with improved biocompatibility and enhanced functionality.
The self-assembly of multifunctional polyesters in the aqueous environment was investigated. The effects of polyester chemical structure and the adopted self-assembly approach on the self-assembly of multifunctional polyesters were examined.
A novel self-amplifying RNA (saRNA) delivery platform based on cationic PEGylated polyesters has been developed. The effects of amine position in a polyester chain on saRNA delivery were studied. The effects of positive charge density and molecular weight of the polyester on saRNA delivery were further investigated. The long-term thermostability of the optimal saRNA-loaded polymeric nanoparticles was evaluated.
A series of sequence-controlled multifunctional polyesters with different molecular wights and block sequences were designed and synthesised for effective saRNA delivery. The effects of polyester molecular weight and block sequence on self-assembly and cell transfection were investigated. The long-term thermostability of the optimal micelleplexes was assessed.
A series of sequence-controlled multifunctional polyesters were employed for intestinal drug delivery via oral administration. Due to the unique pH-responsiveness of the polyesters, drugs were retained within the self-assembled polymeric nanoparticles in acidic aqueous environments like gastric fluids, but were partially released in relatively neutral or basic aqueous solutions like intestinal fluids. The long-term colloidal stability of the polymeric nanoparticles was investigated.
Version
Open Access
Date Issued
2024-10-02
Date Awarded
2025-02-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Chen, Rongjun
Publisher Department
Chemical Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)