SMARTNANO: Enzyme Sensitive Protein-Based Drug Nanocarriers (ProNCs) for Reprogramming of Pancreatic Ductal Adenocarcinoma (PDAC).
Lead Research Organisation:
University of Cambridge
Department Name: Chemical Engineering and Biotechnology
Abstract
Cancer is a huge societal challenge in Europe, as despite sheltering less than 10% of the population, a quarter of all cases worldwide
are diagnosed here.
SMARTNANO will help to fulfill HorizonEurope's mission against cancer by increasing knowledge about this disease, specifically about
one of the most aggressive, pancreatic cancer, and more specifically about its tumor microenvironment (TME). Thus, the Applicant
will do its bit in optimizing treatments and speeding up the translation of drugs.
Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous tumor with a complex microenvironment (stroma) of
noncancerous cells and an extracellular matrix rich in enzymes such as metalloproteases (MMPs). It is also characterized by a lack of
vascularization, resulting in severe hypoxia, which contributes to cancer stemness and angiogenesis. Altogether leads to low
efficiency of chemo/radiotherapy, resistance of cancer cells, evasion of immune system and metastasis.
SMARTNANO aims to overcome the existing limitation of PDAC therapy by employing active protein-based nanoparticles (ProNC)
that simultaneously alleviate hypoxia and deliver stromal reprogramming compounds in a controlled manner, harnessing
metalloproteases from the TME. Therefore, cancer cells will be more susceptible to conventional chemotherapy and elimination by
own immune system. In addition, SMARTNANO will develop the first valuable in vitro human platform for preclinical studies of PDAC
therapeutics, in terms of gender-differentiated organoid co-cultures that closely mimic the TME.
This ambitious high-risk, high-reward project will promote the multidisciplinarity of the applicant's research career, helping her
become a leader of the future, thanks to the carefully designed career development plan in which her learning in tumor biology and
nanoparticle synthesis through engineering techniques, are mixed with training in transfer, leadership and intellectual protection.
are diagnosed here.
SMARTNANO will help to fulfill HorizonEurope's mission against cancer by increasing knowledge about this disease, specifically about
one of the most aggressive, pancreatic cancer, and more specifically about its tumor microenvironment (TME). Thus, the Applicant
will do its bit in optimizing treatments and speeding up the translation of drugs.
Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous tumor with a complex microenvironment (stroma) of
noncancerous cells and an extracellular matrix rich in enzymes such as metalloproteases (MMPs). It is also characterized by a lack of
vascularization, resulting in severe hypoxia, which contributes to cancer stemness and angiogenesis. Altogether leads to low
efficiency of chemo/radiotherapy, resistance of cancer cells, evasion of immune system and metastasis.
SMARTNANO aims to overcome the existing limitation of PDAC therapy by employing active protein-based nanoparticles (ProNC)
that simultaneously alleviate hypoxia and deliver stromal reprogramming compounds in a controlled manner, harnessing
metalloproteases from the TME. Therefore, cancer cells will be more susceptible to conventional chemotherapy and elimination by
own immune system. In addition, SMARTNANO will develop the first valuable in vitro human platform for preclinical studies of PDAC
therapeutics, in terms of gender-differentiated organoid co-cultures that closely mimic the TME.
This ambitious high-risk, high-reward project will promote the multidisciplinarity of the applicant's research career, helping her
become a leader of the future, thanks to the carefully designed career development plan in which her learning in tumor biology and
nanoparticle synthesis through engineering techniques, are mixed with training in transfer, leadership and intellectual protection.
| Description | Nanoparticles were developed composed of natural protein, which can carry oxygen into the core of solid tumour low of oxygen. In this way, nanocarriers can improve the effectiveness of delivered drugs. In addition, 3D models of low-oxygen environment have been developed which will be used in follow up research. |
| Exploitation Route | Models will be published and available to others to use. It is a first type of useful models that mimic low-oxygen regions of solid tumours. Nanoparticles will be used for formulations and further developed by PhD student co-funded by Astra Zeneca |
| Sectors | Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| Description | Developed 3 D models of low-oxygen cores of solid tumours will have significant impact on testing of hypoxia-mediating systems. Significant challenges needed to be overcome to deal with oxygen detection. Finally, a collaboration was established with molecular biologist to obtain cells that change fluorescence depending on the level of oxygen. |
| First Year Of Impact | 2025 |
| Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal Economic |
| Description | Fluorescent hypoxia detecting cells |
| Organisation | University of Cambridge |
| Department | Cambridge Stem Cell Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | developed nanoparticle based system to deliver oxygen to oxygen-low core of solid tumours. This system can enable improved treatment of solid tumours such as pancreatic cancer and deal with common resistance to widely used chemotherapies. |
| Collaborator Contribution | Collaborator provided fluorescent cells, which were incorporated within 3D models of pancreatic cancer and were able to signal the presence and absence of oxygen. |
| Impact | Multi-disciplinary collaboration resulted in development of new 3D model, first of its kind, which can be used by other researchers in development of more efficient therapies for solid tumours. |
| Start Year | 2024 |
| Description | PhD studentship Astra Zeneca |
| Organisation | AstraZeneca |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | we will develop protein nano carriers for solid tumours to explore new formulation for drug delivery |
| Collaborator Contribution | partner will co-fund a studentship to explore delivery and provide targets, models and cargos to deliver into solid tumours. |
| Impact | Co-funding of the PhD student |
| Start Year | 2025 |
| Description | Protein Nanocarriers for Intrapleural Delivery of Therapeutic Cargo and Improved Treatment of Pleural Mesothelioma |
| Organisation | University of Cambridge |
| Department | Department of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We teamed up with Stefan Marciniak to make use of the recently discovered biomarker for lung mesothelioma, and develop drug delivery systems exploiting this biomarker. We have submitted the joint grant to EraseMeso foundation. |
| Collaborator Contribution | The partners provided us with a biomarker and 3D models to test our delivery system. |
| Impact | Grant submission to EraseMeso Foundation. Multi-displinary collaboration between our group and group of Prof. Stefan Marciniak who is working on lung mesothelioma. |
| Start Year | 2024 |
| Description | Invited lecture at RSC Chemical Nanoscience and Nanotechnology Symposium |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited lecture at the annual symposium in London. More than 100 participants attended the symposium, which resulted in new collaboration related to quantum sensors in biomedicine. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.rsc.org/events/detail/76838/rsc-chemical-nanoscience-and-nanotechnology-network-annual-s... |
| Description | Keynote Lecture Ruzicka Days |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Keynote lecture at bi-annual meeting of Croatian chemists and chemical engineers. More than 100 people attended including heads of departments and industry representatives. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.ruzickadays.eu/programme.html |
| Description | Norwegian Biophysics Symposium Keynote lecture |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Keynote lecture of design of nanostructures at the Norwegian Biophysics Symposium. The lecture resulted in a collaboration and a paper which will be submitted this year. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://sites.google.com/view/stroehllab/learning/biophysics-symposium-2024 |
| Description | Prometej- science show on Croatian National TV |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | PI was invited to be the main guest within the prominent science TV show on Channel 1 of Croaitan National TV. Early detection of cancer, including design of the biosensor was discussed. |
| Year(s) Of Engagement Activity | 2024 |