Project: Nanopolymer-Mediated Delivery of Microbial Secondary Metabolites for the Reduction of Non-Small Cell Lung Cancer Aggressiveness
Challenge Space
Food - Precision Fermentation
Prinicipal Investigator(s) and team names
Dr Federico Cerrone (co-PI); Dr Caroline Geoghegan (co-PI), Dr Darren Fayne, PhD student
Collaborating Institutions
University of Southern Denmark (SDU)
Funding support
Orla Benson Foundation
Project start date
1 November 2026
End date
1 November 2030
Problem
Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC) is its most common form.
Beneficial bacteria that live naturally in the lungs produce short-chain fatty acids (SCFAs) that can suppress tumour growth, impair cancer cell survival and enhance the effectiveness of chemo-immunotherapy, but these natural compounds are not produced in sufficient quantity, and delivering them safely and directly to lung tumours remains a major challenge.
On the other hand, cancer patients are also characterised by a weakened immunological system after repeated cycles of chemo and radiotherapy, and they would greatly benefit from a preventative immunostimulation boost when undergoing immuno-weakening sessions.
Background
Microbial adaptations (bacterial and fungi) are characterised by biosynthesis of a plethora of chemical compounds arising from the co-evolution of metabolic pathways that crosstalk with the human host, along gut-to-lung axis and gut-to-brain axis.
A partially overlooked bacterial microbiota is also found resident and increasingly characterised as being adapted to the upper airways’ tracts and lungs according to variable gradients of oxygen. Microaerophilic bacteria are able to produce short chain fatty acids (SCFA) that have a proven effect in reducing cancer aggressiveness by reverting the EMT pathways towards epithelial features.
In addition to that, edible filamentous fungi with an attractive secondary metabolites production and with the ability to produce structural polysaccharides that have immunostimulant properties (generically named: pathogen associated molecular patterns, PAMP, of which α and β-glucans of different branching nature are one of the major compounds).
The careful microbiological understanding of the microbial environmental adaptation and physiology allow to expand the range of production of these microbial secondary metabolites. The most efficient methodology to boost this production is by means of precision fermentation that allow a joint valorisation of renewable carbon sources towards the production of functional ingredients that can have both a therapeutic potential and a reduced carbon footprint.
The production of the secondary metabolites is just half of the picture, a careful and targeted nanoencapsulation together with a precise computational modelling of the uptake can both enhance the stability of the active ingredient for the targeted delivery and for a prolonged uptake and successful therapeutic potential.
Solution
This project will use sustainable precision fermentation to produce high-value microbial metabolites - SCFAs and immunogenic fungal polysaccharides - from renewable carbon sources, and will design custom “nanolipids” delivery vehicles, engineered through advanced computational modelling, to transport these molecules directly into the lung tumour environment.
The resulting therapies will be evaluated in established lung cancer cell models with the SDU partner. The ultimate goal is a non-invasive, highly targeted treatment that halts tumour progression and improves patient outcomes, while advancing sustainable, high-purity manufacturing processes