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Nanotherapeutic platform for lysosomal targeted technology

Project description

Tackling undruggable cancer targets

Cells break down unwanted or damaged macromolecules in specialised organelles called lysosomes. Lysosomal targeting chimeras (LYTACs) are novel molecules that exploit this pathway to selectively degrade disease-causing proteins. This strategy also holds promise against cancer proteins that are inaccessible to conventional drugs. With the support of the Marie Skłodowska-Curie Actions programme, the Nano-LYTAC project combines LYTACs with nanotechnology to enhance their tumour specificity, bioavailability, and stability. Researchers aim to engineer nanoparticles that protect and selectively release LYTACs in the tumour microenvironment. This project will provide proof of concept for a LYTAC-mediated therapy against cancer.

Objective

"Cancer remains a tough challenge, largely because 80% of cancer-driving proteins are considered “undruggable” meaning impossible to target with conventional therapies. Nano-LYTAC project brings together experts in nanomedicine, pharmaceutical technology, and nanotoxicology to answer the burning question: Does complete cancer eradication still remain as an elusive dream? By combining 2 cutting-edge technologies: “Smart Nanotechnology” and “Targeted Protein Degraders (TPDs)”, this project fulfills the goals of Europe’s Beating Cancer Plan by tackling these undruggable proteins. TPDs were created using Nobel Prize-winning bioorthogonal chemistry. Among these, LYTACs (Lysosomal Targeting Chimeras), with their ability to transport intracellular/extracellular cancer-driving protein for selective degradation in the lysosomes, abrogate the cancer pathology. However, despite their promise, LYTACs haven’t made it to clinical use yet, owing to challenges like limited molecule diversity, poor tumor penetration, low bioavailability, and metabolic instability. To transform LYTACs into clinically viable cancer therapies, and to overcome the aforementioned drawbacks, this project will use novel nanotechnological approach to enable enhanced tumor penetration, selectivity, protection, and controlled released of the LYTACs in tumor microenvironment. Moreover, for the first time, I will design new LYTAC molecules specifically targeting folate receptors that are overexpressed on many types of cancers (e.g.: breast cancers, lung cancer, ovarian cancers). At CATRIN, under the guidance of Prof. Kateřina Poláková, an expert in nanomedicine and their subcellular trafficking, and nanotoxicology, I will develop ""Smart Nano-LYTACs"" with the preclinical proof of their potential. This multidisciplinary project will also enhance my skills in nanotherapeutics and cancer biology, helping me to work towards my long-term goal of establishing my own research group focused on advanced cancer therapies."

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERZITA PALACKEHO V OLOMOUCI
Net EU contribution
€ 207 758,16
Address
KRIZKOVSKEHO 8
771 47 Olomouc
Czechia
Region
Česko Střední Morava Olomoucký kraj
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Partners (1)