Study of thermo-responsive polymer-drug conjugates
Loading...
Date
2025-03-07
Authors
Συγκούνα, Αναστασία
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Cancer is one of the deadliest diseases of the 21st century, with traditional treatments such as chemotherapy often associated with severe side effects and significant limitations. One commonly used chemotherapy drug is gemcitabine, a prodrug effective against various solid tumours. However, its clinical application is hindered by a short plasma half-life, systemic toxicities and the development of resistance.
To overcome these challenges, there is a pressing need to develop more effective and targeted cancer treatment strategies. Targeted therapy aims to enhance drug concentration in specific regions of the body while minimizing exposure to healthy tissues, thereby improving treatment efficacy and reducing adverse effects. One promising approach to achieving targeted therapy is through nanotech-nology, which allows for precise drug delivery.
This diploma thesis explores the development of self-assembled thermo-responsive polymer-drug conjugates as a novel approach to targeted cancer therapy. Two types of thermo-responsive block copolymers were synthesized, differing in their linker chemistry: one incorporating a non-cleavable succinic anhydride linker and the other a reducible disulfide bond. Both copolymers featured a (MEO2MA-co-OEGMA500) corona, designed to provide stability and responsiveness to external stimuli.
The synthesized polymers were extensively characterized using analytical techniques such as nu-clear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), and dynamic light scattering (DLS) to confirm their structural properties. To evaluate their potential as advanced drug delivery systems, drug release studies were conducted under various conditions, including pH-triggered, temperature-triggered and ultrasound-triggered release.
Moreover, in this work we investigated the role of reactive oxygen species (ROS) in polymer bond cleavage, improving drug release efficiency. To support this, zinc phthalocyanine (ZnPc) was synthe-sized and tested for its ability to generate ROS. DPBF and TPA assays, were conducted to confirm that ZnPc can produce singlet oxygen and hydroxyl radicals. These findings validate the potential of ZnPc as an effective sonosensitizer for ROS-mediated bond cleavage within polymer-drug conjugates.
Overall, this diploma thesis provides valuable insights into the development of smart, stimuli-responsive drug delivery systems, offering new strategies for enhancing the effectiveness of cancer treatment.
Description
Keywords
Thermo-responsive polymer-drug conjugates, Drug delivery system, Gemcitabine, Drug release, Sonosensitizers