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Spatiotemporal control of singlet oxygen release from supramolecular hydrogels to improve cancer therapy

Project description

Targeted hydrogel-based oxygen delivery for cancer therapy

Singlet oxygen (¹O₂) is a high-energy, reactive form of molecular oxygen with electrons in an excited state, making it more chemically active than the ground-state oxygen we breathe. In this excited state, singlet oxygen can react with various organic molecules, leading to oxidation reactions that can damage lipids, proteins, and DNA. This reactivity makes it useful in medical therapies targeting cancer cells or pathogens. With the support of the Marie Skłodowska-Curie Actions programme, the OTHOx project aims to develop novel supramolecular hydrogels as carriers for singlet oxygen. The research team will introduce modular hydrogels carrying endoperoxides rich in singlet oxygen and analyse their properties and safety profile.

Objective

This research aims to develop novel supramolecular hydrogels and study their application as singlet oxygen (1O2) carriers. In medicine, 1O2 generated in-vivo through photochemistry has been used to treat a variety of ailments including bacterial infections, acne, and several types of cancer. Though promising, this approach suffers from drawbacks such as diminished effectiveness in hypoxic conditions, both native and induced and lack of control over the total concentration and dosage of active 1O2. Recently, endoperoxides (EPO) have been identified as a potential solution for those, as they are self-contained sources of 1O2 produced ex-situ. However, they still do not allow for precise spatiotemporal control of 1O2 release, which is desirable to maximize for effectiveness of the treatment. Grafting EPOs on solid supports has been explored as a solution, but the state-of-the-art materials rely on complicated supports with low EPO loadings and thermal release mechanisms. Herein, we propose a new strategy for spatiotemporal control of 1O2 through the unprecedented use of hydrogels as EPO carriers. Hydrogels offer an easy to control and stable, but not persistent matrix in which the main component is water. The OTHO (oxotriphenylhexanoate) hydrogels enjoy unparalleled modularity, due to their highly robust and selective multicomponent one-pot synthesis. Thus, we will synthesize a range of OTHOs containing EPO units and perform detailed studies by rheology, solid-state NMR, small-angle x-ray and neutron scattering and electron microscopy to understand the properties and behavior of the resulting hydrogels. The biocompatibility and cytotoxic profile of the materials will be investigated against yeast cells expressing human disease markers. This will pave the way for a new breed of supramolecular pharmacology materials for 1O2 therapy against cancer.

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Coordinator

GOETEBORGS UNIVERSITET
Net EU contribution
€ 206 887,68
Address
VASAPARKEN
405 30 Goeteborg
Sweden

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Region
Södra Sverige Västsverige Västra Götalands län
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data