Periodic Reporting for period 1 - LCT (Localized Cancer Therapy)
Periodo di rendicontazione: 2023-01-02 al 2025-03-01
Cancer remains one of the most urgent public health challenges facing Europe today. Each year, millions of new cases are diagnosed, with abdominal organ cancers among the most frequent and deadly. Although established treatments such as surgery, chemotherapy, and radiation therapy have significantly improved patient survival, they continue to suffer from fundamental limitations: lack of specificity, severe side effects, and reduced therapeutic efficiency due to drug resistance or poor tumor targeting. These limitations are not merely medical—they carry social, economic, and policy implications, as healthcare systems across the EU are called upon to deliver safer, more effective, and more personalized treatment options.
The Localized Cancer Therapy (LCT) project was launched to address these challenges at their core. Its central goal is to develop a next-generation cancer treatment approach by integrating smart, radiation-responsive drug delivery systems into existing radiotherapy protocols. Specifically, the project focuses on the synthesis of biodegradable, biocompatible polymer-based nanocarriers, tiny, engineered particles that can carry chemotherapy drugs directly to tumors, then release them in a controlled manner when exposed to therapeutic radiation.
This strategy addresses two major needs in current oncology practice. First, it provides spatial precision, ensuring that chemotherapeutic agents are delivered to the tumor site rather than circulating systemically. Second, it enables temporal control, so that drugs are released exactly when they are most effective, during the moment of radiation exposure. By linking drug release to gamma irradiation, LCT envisions a system where the treatment is confined both in time and space, reducing damage to healthy tissues and minimizing side effects.
Beyond drug delivery, the project also tackles a critical technical gap in the field: the mechanical modelling of soft, cancerous tissues in vivo, particularly in the abdomen where respiratory motion complicates treatment planning. Current radiotherapy models often rely on ex vivo or animal data, which limits their accuracy. To overcome this, LCT applies novel experimental techniques such as Cavitation Rheology, supported by computational simulations and advanced material characterization. This interdisciplinary approach allows for more reliable modelling of organ motion and deformation during breathing, paving the way for more accurate and patient-specific radiation targeting.
The expected impacts of the project are significant in both scientific and societal terms. Scientifically, LCT will expand the frontiers of soft matter mechanics, nanomedicine, and computational oncology. It introduces a unique multimodal treatment paradigm that enhances radiotherapy precision while integrating controlled chemotherapy. Societally, it has the potential to reduce the burden on healthcare systems by lowering treatment complications, improving patient outcomes, and creating a foundation for more affordable and accessible cancer care.
Strategically, LCT aligns with the EU’s missions in cancer, health innovation, and personalized medicine, as outlined in the Horizon Europe framework and the Europe’s Beating Cancer Plan. The project contributes to the goals of EU4Health by promoting innovation in cancer care, and it supports Open Science by making its findings publicly available through dedicated platforms and dissemination events.
In summary, the LCT project represents a bold and practical step toward next-generation cancer therapy. It is grounded in rigorous science, shaped by real-world clinical needs, and guided by the conviction that precision, safety, and efficacy should no longer be competing ideals, but mutually reinforcing pillars of modern medicine.
The Localized Cancer Therapy (LCT) project was launched to address these challenges at their core. Its central goal is to develop a next-generation cancer treatment approach by integrating smart, radiation-responsive drug delivery systems into existing radiotherapy protocols. Specifically, the project focuses on the synthesis of biodegradable, biocompatible polymer-based nanocarriers, tiny, engineered particles that can carry chemotherapy drugs directly to tumors, then release them in a controlled manner when exposed to therapeutic radiation.
This strategy addresses two major needs in current oncology practice. First, it provides spatial precision, ensuring that chemotherapeutic agents are delivered to the tumor site rather than circulating systemically. Second, it enables temporal control, so that drugs are released exactly when they are most effective, during the moment of radiation exposure. By linking drug release to gamma irradiation, LCT envisions a system where the treatment is confined both in time and space, reducing damage to healthy tissues and minimizing side effects.
Beyond drug delivery, the project also tackles a critical technical gap in the field: the mechanical modelling of soft, cancerous tissues in vivo, particularly in the abdomen where respiratory motion complicates treatment planning. Current radiotherapy models often rely on ex vivo or animal data, which limits their accuracy. To overcome this, LCT applies novel experimental techniques such as Cavitation Rheology, supported by computational simulations and advanced material characterization. This interdisciplinary approach allows for more reliable modelling of organ motion and deformation during breathing, paving the way for more accurate and patient-specific radiation targeting.
The expected impacts of the project are significant in both scientific and societal terms. Scientifically, LCT will expand the frontiers of soft matter mechanics, nanomedicine, and computational oncology. It introduces a unique multimodal treatment paradigm that enhances radiotherapy precision while integrating controlled chemotherapy. Societally, it has the potential to reduce the burden on healthcare systems by lowering treatment complications, improving patient outcomes, and creating a foundation for more affordable and accessible cancer care.
Strategically, LCT aligns with the EU’s missions in cancer, health innovation, and personalized medicine, as outlined in the Horizon Europe framework and the Europe’s Beating Cancer Plan. The project contributes to the goals of EU4Health by promoting innovation in cancer care, and it supports Open Science by making its findings publicly available through dedicated platforms and dissemination events.
In summary, the LCT project represents a bold and practical step toward next-generation cancer therapy. It is grounded in rigorous science, shaped by real-world clinical needs, and guided by the conviction that precision, safety, and efficacy should no longer be competing ideals, but mutually reinforcing pillars of modern medicine.
The LCT project has made substantial technical progress in developing an integrated, precision-focused approach to abdominal cancer treatment. The research has been structured around three core scientific objectives, each contributing to the broader aim of enhancing the specificity, safety, and effectiveness of cancer therapy through novel nanocarrier design, responsive drug release, and accurate treatment planning. Below is a summary of the key research activities and technical achievements to date.
RO1 – Mechanics of Abdominal Cancerous Tissues:
A comprehensive literature review was conducted to evaluate existing experimental and computational approaches used to model the mechanical behavior of abdominal tissues, particularly under respiratory motion. This review, now under peer review in a scholarly journal, identifies gaps in current methodologies and highlights the importance of in vivo-compatible techniques.
To address these gaps, a series of experiments were conducted using porcine liver tissue—a physiologically relevant model for abdominal organs. These experiments employed techniques such as uniaxial testing and cavitation rheology to characterize nonlinear and anisotropic behavior. Preliminary results were presented at the Advances in Applied Mechanics Conference (Gran Canaria, Spain), where they received positive feedback from the biomechanics community.
In parallel, mechanical testing was performed on fiber-reinforced gels to assess their potential as tissue-mimicking materials for future modelling efforts. The data generated from these studies have been deposited in an open-access repository and summarized in the “Results” module of this reporting system.
RO2 – Multimodal Treatment Using Biodegradable PVA Gel Nanocarriers and Radiation:
A focused research effort was undertaken to investigate the behavior of polyvinyl alcohol (PVA)-based hydrogel nanocarriers under gamma radiation, with an emphasis on their capacity to release encapsulated drugs in a controlled and timely manner. This work involved fabricating nanocarriers through emulsion methods and assessing drug release kinetics under different irradiation conditions.
The results confirmed the hypothesis that gamma irradiation can serve as an effective external trigger for controlled drug release, supporting the feasibility of combining radiotherapy with targeted chemotherapy. These findings have been documented in the “Results” module and are currently being prepared for publication in a dedicated manuscript.
RO3 – Detecting Nanocarriers and Tumours for Targeted Delivery:
Following detailed discussions during the secondment period, the original plan to use carbon nanotubes as contrast agents was revised in favor of iron oxide (Fe2O3) nanoparticles, due to their superior biocompatibility, availability, and established safety profile in medical imaging.
Subsequent investigations focused on integrating Fe2O3 nanoparticles with PVA hydrogel nanocarriers to create a dual-function platform capable of both drug delivery and magnetic resonance imaging (MRI) contrast enhancement. Preliminary results indicate successful surface modification and stable conjugation between the two nanoparticle systems. This integrated platform offers a promising route for simultaneous tumor localization and therapeutic delivery, a critical step toward real-time image-guided cancer treatment.
RO1 – Mechanics of Abdominal Cancerous Tissues:
A comprehensive literature review was conducted to evaluate existing experimental and computational approaches used to model the mechanical behavior of abdominal tissues, particularly under respiratory motion. This review, now under peer review in a scholarly journal, identifies gaps in current methodologies and highlights the importance of in vivo-compatible techniques.
To address these gaps, a series of experiments were conducted using porcine liver tissue—a physiologically relevant model for abdominal organs. These experiments employed techniques such as uniaxial testing and cavitation rheology to characterize nonlinear and anisotropic behavior. Preliminary results were presented at the Advances in Applied Mechanics Conference (Gran Canaria, Spain), where they received positive feedback from the biomechanics community.
In parallel, mechanical testing was performed on fiber-reinforced gels to assess their potential as tissue-mimicking materials for future modelling efforts. The data generated from these studies have been deposited in an open-access repository and summarized in the “Results” module of this reporting system.
RO2 – Multimodal Treatment Using Biodegradable PVA Gel Nanocarriers and Radiation:
A focused research effort was undertaken to investigate the behavior of polyvinyl alcohol (PVA)-based hydrogel nanocarriers under gamma radiation, with an emphasis on their capacity to release encapsulated drugs in a controlled and timely manner. This work involved fabricating nanocarriers through emulsion methods and assessing drug release kinetics under different irradiation conditions.
The results confirmed the hypothesis that gamma irradiation can serve as an effective external trigger for controlled drug release, supporting the feasibility of combining radiotherapy with targeted chemotherapy. These findings have been documented in the “Results” module and are currently being prepared for publication in a dedicated manuscript.
RO3 – Detecting Nanocarriers and Tumours for Targeted Delivery:
Following detailed discussions during the secondment period, the original plan to use carbon nanotubes as contrast agents was revised in favor of iron oxide (Fe2O3) nanoparticles, due to their superior biocompatibility, availability, and established safety profile in medical imaging.
Subsequent investigations focused on integrating Fe2O3 nanoparticles with PVA hydrogel nanocarriers to create a dual-function platform capable of both drug delivery and magnetic resonance imaging (MRI) contrast enhancement. Preliminary results indicate successful surface modification and stable conjugation between the two nanoparticle systems. This integrated platform offers a promising route for simultaneous tumor localization and therapeutic delivery, a critical step toward real-time image-guided cancer treatment.
The LCT project has generated promising technical results that move beyond current practice in cancer treatment and soft tissue modeling. The work introduces innovations across biomechanics, materials engineering, and radiation-enhanced drug delivery, all with direct relevance to next-generation therapeutic strategies.
1. Enhanced Understanding of In Vivo Tissue Mechanics
A key advancement lies in the extension of cavitation rheology to model the nonlinear, anisotropic behavior of abdominal tissues. Unlike conventional methods that rely on ex vivo samples or animal approximations, this work enables more accurate in silico simulations of organ motion under respiration, a critical factor for improving radiotherapy precision. The methodology is grounded in new data generated from porcine liver and synthetic gels, offering a framework for future patient-specific models. This advancement supports clinical goals in adaptive radiation planning and addresses a longstanding bottleneck in computational oncology.
2. Radiation-Triggered Drug Delivery via PVA Nanocarriers
The project has demonstrated that PVA hydrogel nanocarriers can respond to gamma radiation by releasing encapsulated drugs in a controlled manner. This finding establishes a clear technical pathway toward integrating chemotherapy with radiotherapy in a single, localized session—minimizing systemic toxicity and improving therapeutic index. These nanocarriers are biocompatible, biodegradable, and tunable, making them suitable for a range of clinical settings. The approach meets the demand for safer, more personalized treatment modalities and contributes to the development of precision oncology tools.
3. MRI-Compatible Dual-Function Nanoplatforms
By substituting carbon nanotubes with iron oxide nanoparticles, the project successfully developed a dual-function nanoplatform capable of both imaging and therapeutic functions. The integration of PVA carriers with Fe2O3 particles addresses safety concerns while enhancing MRI visibility, enabling real-time localization of the drug delivery vehicle. This work directly supports clinical translation efforts in image-guided therapy and opens new possibilities for non-invasive treatment monitoring.
1. Enhanced Understanding of In Vivo Tissue Mechanics
A key advancement lies in the extension of cavitation rheology to model the nonlinear, anisotropic behavior of abdominal tissues. Unlike conventional methods that rely on ex vivo samples or animal approximations, this work enables more accurate in silico simulations of organ motion under respiration, a critical factor for improving radiotherapy precision. The methodology is grounded in new data generated from porcine liver and synthetic gels, offering a framework for future patient-specific models. This advancement supports clinical goals in adaptive radiation planning and addresses a longstanding bottleneck in computational oncology.
2. Radiation-Triggered Drug Delivery via PVA Nanocarriers
The project has demonstrated that PVA hydrogel nanocarriers can respond to gamma radiation by releasing encapsulated drugs in a controlled manner. This finding establishes a clear technical pathway toward integrating chemotherapy with radiotherapy in a single, localized session—minimizing systemic toxicity and improving therapeutic index. These nanocarriers are biocompatible, biodegradable, and tunable, making them suitable for a range of clinical settings. The approach meets the demand for safer, more personalized treatment modalities and contributes to the development of precision oncology tools.
3. MRI-Compatible Dual-Function Nanoplatforms
By substituting carbon nanotubes with iron oxide nanoparticles, the project successfully developed a dual-function nanoplatform capable of both imaging and therapeutic functions. The integration of PVA carriers with Fe2O3 particles addresses safety concerns while enhancing MRI visibility, enabling real-time localization of the drug delivery vehicle. This work directly supports clinical translation efforts in image-guided therapy and opens new possibilities for non-invasive treatment monitoring.