Periodic Reporting for period 2 - PERSEUS (2D Material-Based Multiple Oncotherapy Against Metastatic Disease Using a Radically New ComputedTomography Approach)
Berichtszeitraum: 2024-03-01 bis 2025-08-31
Cancer is a major global health challenge. Europe accounts for a quarter of all cases despite having only 10% of the world’s population. According to Europe’s Beating Cancer Plan, cancer-related deaths are projected to rise by over 24% by 2035, highlighting the urgent need for new strategies in prevention, treatment, and care.
Radiation therapy and phototherapy are often preferred over surgery for their minimally invasive nature. However, radiation can damage healthy cells and cause severe side effects, including secondary tumours and organ damage. Light-based treatments also struggle with deep-seated tumours due to limited tissue penetration.
PERSEUS introduces a ground-breaking approach for treating some of the most aggressive and deep-seated cancers, including pancreatic ductal adeno carcinoma, triple-negative breast, liver and colorectal cancers, as well as their metastases. It leverages an innovative nanotechnology-based therapy using nanosystems (NS) activated by low-dose, low-energy CT beams. These NSs enhance soft X-ray absorption and locally convert X-rays into two simultaneous therapies: (1) generation of reactive oxygen species (ROS), which kill tumour cells and sensitize them to radiation, and (2) increase direct DNA interaction through radiolysis and radiosensitization. These processes disrupt cell integrity—damaging proteins, nucleic acids and membranes—triggering necrosis, apoptosis, and blocking DNA replication.
The NSs are encapsulated into liposomes, tiny synthetic vesicles that serve as delivery vehicles, navigating through the vascular system to specifically target tumour masses.
Unlike conventional methods, low energy/low dose X-rays (e.g. from a CT beam) are used to activate the NSs after targeting the tumour. The NSs can either be injected directly inside the tumour or delivered through the bloodstream to reach the tumour site. Hence, the NS contributes to eliminating cancer cells by generating radiosensitization, thereby boosting the effect of low dose/low energy radiotherapy thanks to its physico-chemical properties, which are strictly tied to the NS design. Since ROS and other reactive species produced through increased radiosensitization are cancerogenic agents whose efficacy does not depend on cell type, the therapy is agnostic to cancer type and gender incidence.
The cell death occurs directly into the tumour mass, minimizing damage to healthy tissue and reducing side effects. The treatment can even help the body's immune system to recognize and fight cancer at distal sites from the primary tumour (abscopal effect). The NSs are designed to be biocompatible and inactive in absence of X-ray radiation, thus allowing a safe body clearance (the ability of an organ to purify from a substance in the time unit).
Overall objectives:
- Development of the NSs having the optimal size and the desired X-ray induced physical properties
- Assessment and validation of the NSs design, efficacy and safety through in vitro experiments
- Pre-clinical proof-of-concept of NSs for cancer therapy in in vivo models
- Pre-clinical treatment of metastases
Radiation therapy and phototherapy are often preferred over surgery for their minimally invasive nature. However, radiation can damage healthy cells and cause severe side effects, including secondary tumours and organ damage. Light-based treatments also struggle with deep-seated tumours due to limited tissue penetration.
PERSEUS introduces a ground-breaking approach for treating some of the most aggressive and deep-seated cancers, including pancreatic ductal adeno carcinoma, triple-negative breast, liver and colorectal cancers, as well as their metastases. It leverages an innovative nanotechnology-based therapy using nanosystems (NS) activated by low-dose, low-energy CT beams. These NSs enhance soft X-ray absorption and locally convert X-rays into two simultaneous therapies: (1) generation of reactive oxygen species (ROS), which kill tumour cells and sensitize them to radiation, and (2) increase direct DNA interaction through radiolysis and radiosensitization. These processes disrupt cell integrity—damaging proteins, nucleic acids and membranes—triggering necrosis, apoptosis, and blocking DNA replication.
The NSs are encapsulated into liposomes, tiny synthetic vesicles that serve as delivery vehicles, navigating through the vascular system to specifically target tumour masses.
Unlike conventional methods, low energy/low dose X-rays (e.g. from a CT beam) are used to activate the NSs after targeting the tumour. The NSs can either be injected directly inside the tumour or delivered through the bloodstream to reach the tumour site. Hence, the NS contributes to eliminating cancer cells by generating radiosensitization, thereby boosting the effect of low dose/low energy radiotherapy thanks to its physico-chemical properties, which are strictly tied to the NS design. Since ROS and other reactive species produced through increased radiosensitization are cancerogenic agents whose efficacy does not depend on cell type, the therapy is agnostic to cancer type and gender incidence.
The cell death occurs directly into the tumour mass, minimizing damage to healthy tissue and reducing side effects. The treatment can even help the body's immune system to recognize and fight cancer at distal sites from the primary tumour (abscopal effect). The NSs are designed to be biocompatible and inactive in absence of X-ray radiation, thus allowing a safe body clearance (the ability of an organ to purify from a substance in the time unit).
Overall objectives:
- Development of the NSs having the optimal size and the desired X-ray induced physical properties
- Assessment and validation of the NSs design, efficacy and safety through in vitro experiments
- Pre-clinical proof-of-concept of NSs for cancer therapy in in vivo models
- Pre-clinical treatment of metastases
During the first year of the project, the PERSEUS team identified the best 2D material candidates for the NS fabrication, and 2D nanoflakes were fabricated with the required size to be incorporated into liposomes. Additionally, the team successfully functionalized them to enhance the NS effectiveness in cancer treatment.
To determine the optimal materials for the NS, theoretical simulations were performed to assess the X-ray absorption rates of the various candidates and therefore to select the material with the highest absorption capacity which is correlated to more effective cancer treatment.
Furthermore, the consortium conducted a preliminary test on ROS generation - one of the two cancer-killing therapies designed for the NS - in cancer cell lines. Remarkably, following NS uptake, human colon adenocarcinoma cells treated with X-ray irradiation exhibited 25-30% more ROS production compared to untreated samples.
The NSs were found to be biocompatible, and no endotoxin contamination was detected. Moreover, NS components were successfully incorporated into lipid nanoparticles using a novel strategy.
Additionally, in the first year an Expert Advisory board was organised to obtain strategic and independent advice and to ensure PERSEUS can have maximum impact for the public benefit.
Building on the achievements of the first year, the project has advanced significantly, with new steps taken to optimize and validate the NS for cancer treatment.
- The NS was further refined to achieve optimal structural and functional properties, enhancing its ability to work effectively under low-energy/low dose X-ray irradiation.
- A new encapsulation strategy was developed, enabling selective targeting of cancer cells. Tests confirmed that the NS shows strong cancer-killing potential when combined with low-energy/low dose X-ray irradiation in both 2D and 3D tumour models.
- In-vivo studies demonstrated the NS biocompatibility and biodegradability, as well as its ability to accumulate in specific organs and to target tumours effectively.
- Biodistribution and safety studies were expanded to include pancreatic and breast cancer models, further supporting the NS’s potential for broad therapeutic applications.
To determine the optimal materials for the NS, theoretical simulations were performed to assess the X-ray absorption rates of the various candidates and therefore to select the material with the highest absorption capacity which is correlated to more effective cancer treatment.
Furthermore, the consortium conducted a preliminary test on ROS generation - one of the two cancer-killing therapies designed for the NS - in cancer cell lines. Remarkably, following NS uptake, human colon adenocarcinoma cells treated with X-ray irradiation exhibited 25-30% more ROS production compared to untreated samples.
The NSs were found to be biocompatible, and no endotoxin contamination was detected. Moreover, NS components were successfully incorporated into lipid nanoparticles using a novel strategy.
Additionally, in the first year an Expert Advisory board was organised to obtain strategic and independent advice and to ensure PERSEUS can have maximum impact for the public benefit.
Building on the achievements of the first year, the project has advanced significantly, with new steps taken to optimize and validate the NS for cancer treatment.
- The NS was further refined to achieve optimal structural and functional properties, enhancing its ability to work effectively under low-energy/low dose X-ray irradiation.
- A new encapsulation strategy was developed, enabling selective targeting of cancer cells. Tests confirmed that the NS shows strong cancer-killing potential when combined with low-energy/low dose X-ray irradiation in both 2D and 3D tumour models.
- In-vivo studies demonstrated the NS biocompatibility and biodegradability, as well as its ability to accumulate in specific organs and to target tumours effectively.
- Biodistribution and safety studies were expanded to include pancreatic and breast cancer models, further supporting the NS’s potential for broad therapeutic applications.
In vitro proliferation inhibition of human colon adenocarcinoma cells (HT29) was for the first time proved through effective ROS generation from our NS, under low energy continuous X-ray irradiation, as compared to untreated-unirradiated samples.
Building on the initial proof of concept, selective targeting of cancer cells was successfully demonstrated and strong cancer-killing efficacy was confirmed in both 2D and 3D tumour models. In-vivo studies further validated the nanosystem’s safety, biodegradability, and tumour-targeting potential, marking an important step toward future clinical translation
Building on the initial proof of concept, selective targeting of cancer cells was successfully demonstrated and strong cancer-killing efficacy was confirmed in both 2D and 3D tumour models. In-vivo studies further validated the nanosystem’s safety, biodegradability, and tumour-targeting potential, marking an important step toward future clinical translation