Periodic Reporting for period 1 - TheraTools (Innovative tools to treat and model complex cancer environments)
Período documentado: 2023-01-01 hasta 2024-12-31
TheraTools has arisen as a multidisciplinary research and training network that encompasses a full academical and technological view of the development of scientific tools for the comprehensive research of malignant tumors localized beyond a biological barrier, as in brain tumors. This challenging objective needs of the concerted effort of both academic and industrial organizations. As such, TheraTools is formed by a consortium composed by (a) four academic beneficiaries (POLYMAT-University of the Basque Country, Spain; University of Aveiro, Portugal; Italian Institute of Technology, linked to Sant´Anna School of Advanced Studies, Italy, and Technion – Israel Institute of Technology, Israel). All the partners will be involved in both research and training activities framed within this network.
Specifically, TheraTools doctoral network has been carefully tailored to set up a supportive environment that instructs future leaders in the area of the development and validation of therapeutics, covering research and training areas that include biochemistry, polymer chemistry, microfluidics, 3D printing, biology, drug delivery, fabrication of cancer models, cell biology, and therapeutics. The participation of the consortium of several industrial partners makes TheraTools highly intersectorial and provides the opportunity to young researchers to follow the industrial path of the products/services that they develop in the laboratory.
TheraTools consortium aims to develop novel strategies to ensure an effective transport of biomacromolecular therapeutics across biological barriers, while protecting them from protease degradation/denaturation and allowing their sustained release at the target site to avoid off-target side-effects. In parallel, TheraTools aims at assembling biomimetic real-scale models including vascularised tumors (and not individualized cancer cells) and sensors in close proximity of the cells to facilitate temporal and spatial resolution of cell-cell and cell-therapeutic interactions, which could pave the way towards monitoring the dynamic tumor responses with much higher accessibility compared to current in vitro and in vivo models.
Specifically, TheraTools doctoral network has been carefully tailored to set up a supportive environment that instructs future leaders in the area of the development and validation of therapeutics, covering research and training areas that include biochemistry, polymer chemistry, microfluidics, 3D printing, biology, drug delivery, fabrication of cancer models, cell biology, and therapeutics. The participation of the consortium of several industrial partners makes TheraTools highly intersectorial and provides the opportunity to young researchers to follow the industrial path of the products/services that they develop in the laboratory.
TheraTools consortium aims to develop novel strategies to ensure an effective transport of biomacromolecular therapeutics across biological barriers, while protecting them from protease degradation/denaturation and allowing their sustained release at the target site to avoid off-target side-effects. In parallel, TheraTools aims at assembling biomimetic real-scale models including vascularised tumors (and not individualized cancer cells) and sensors in close proximity of the cells to facilitate temporal and spatial resolution of cell-cell and cell-therapeutic interactions, which could pave the way towards monitoring the dynamic tumor responses with much higher accessibility compared to current in vitro and in vivo models.
TheraTools project has been working to pursue the following research objectives:
O1. To find a therapeutic approach that enables the treatment of severe pathologies localized beyond biological barriers. The delivery system will have the ability to shield the antibodies from external environment and to release them under tumoral environment; and O2. To reduce the use of animal models for the screening of therapeutic drugs. Models will be focused on GBM.
The main progress to achieve O1 include:
- The synthesis and full characterization of 6 types of polymeric-based drug nano-/microcarriers in which antibodies can be deliver
- Peptide-sensitive nanogels based on polyglycerol dendrimers highly loaded with cetuximab have been synthesized and charcterized
- The protocol for the antibody-wrapped peptide-sensitive nanogels is established.
- The protocol for the synthesis of nanoparticles based on platelet lysates is ready.
- Nanoparticles made out of self-assembled copolymers with conjugated antibody are ready to be tested
- Nanoparticles made out of sono-responsive self-assembled copolymers are ready to be tested
- Multilayered systems with sono-responsive behaviour have been built and characterized
- First experiments assessing the tumor penetrability and anticancer activity in vitro have been performed for some systems
The main progress to achieve O2 include:
- Significant strides have been done in the use of microfluidics to resemble the GBM environment.
- We have successfully built a sensing platform to monitor solid tumors (sensing performance is currently being assessed)
- The basis to fabricate devices that mimic the BBB using microfluidics has been established
- 2-chamber devices and hiPSCs, specific differentiation into the most relevant cells in the BBB has been achieved
- 3D models are being built, including the fabrication of microtubes that resemble the vasculature of solid tumors and optimized coaxial models that integrate multicellular dimensions to the GMB models.
O1. To find a therapeutic approach that enables the treatment of severe pathologies localized beyond biological barriers. The delivery system will have the ability to shield the antibodies from external environment and to release them under tumoral environment; and O2. To reduce the use of animal models for the screening of therapeutic drugs. Models will be focused on GBM.
The main progress to achieve O1 include:
- The synthesis and full characterization of 6 types of polymeric-based drug nano-/microcarriers in which antibodies can be deliver
- Peptide-sensitive nanogels based on polyglycerol dendrimers highly loaded with cetuximab have been synthesized and charcterized
- The protocol for the antibody-wrapped peptide-sensitive nanogels is established.
- The protocol for the synthesis of nanoparticles based on platelet lysates is ready.
- Nanoparticles made out of self-assembled copolymers with conjugated antibody are ready to be tested
- Nanoparticles made out of sono-responsive self-assembled copolymers are ready to be tested
- Multilayered systems with sono-responsive behaviour have been built and characterized
- First experiments assessing the tumor penetrability and anticancer activity in vitro have been performed for some systems
The main progress to achieve O2 include:
- Significant strides have been done in the use of microfluidics to resemble the GBM environment.
- We have successfully built a sensing platform to monitor solid tumors (sensing performance is currently being assessed)
- The basis to fabricate devices that mimic the BBB using microfluidics has been established
- 2-chamber devices and hiPSCs, specific differentiation into the most relevant cells in the BBB has been achieved
- 3D models are being built, including the fabrication of microtubes that resemble the vasculature of solid tumors and optimized coaxial models that integrate multicellular dimensions to the GMB models.
The results achieved in the framework of TheraTools are innovative and will undoubtedly impact the field of biomaterial science. Besides research articles published, one patent application has been filled. Here the details of the outcomes achieved:
- (scientific paper): Sensorization of Microfluidic Brain-on-a-Chip Devices: Towards a New Generation of Integrated Drug Screening Systems (Trends in Analytical Chemistry, 2023, DOI: 10.1016/j.trac.2023.117319). This review collects the state-of-the-art methodologies used to sensor brain-on-a-chip devices that are sensorized. In TheraTools, advanced sensoring systems beyond the current strategies have been developed (WP3) and will be published shortly.
- (scientific paper): Inorganic Sonosensitizer Nanomaterials for Sonodynamic Therapy of Diseases Beyond Cancer (DOI: 10.1016/j.pmatsci.2024.101384). This review encompasses different materials used as sonsosensitazers for therapy. This review has an impact in the WP2, in which sono-responsive materials have been synthesized and mill be tested in different models within the consortium.
- (patent application): Device for monitoring the growth of a three-dimensional cell cluster and method of its manufacture (Filing date: 22.07.2024 Priority Number: 102024000016873). The tasks developed in the TheraTools project have provided the development of innovative devices to monitor cell clusters, which might impact the development of cellular models to screen drugs. The successful implementation of these devices might have an impact on 3R guides of the use of animal models.
- (scientific paper): Sensorization of Microfluidic Brain-on-a-Chip Devices: Towards a New Generation of Integrated Drug Screening Systems (Trends in Analytical Chemistry, 2023, DOI: 10.1016/j.trac.2023.117319). This review collects the state-of-the-art methodologies used to sensor brain-on-a-chip devices that are sensorized. In TheraTools, advanced sensoring systems beyond the current strategies have been developed (WP3) and will be published shortly.
- (scientific paper): Inorganic Sonosensitizer Nanomaterials for Sonodynamic Therapy of Diseases Beyond Cancer (DOI: 10.1016/j.pmatsci.2024.101384). This review encompasses different materials used as sonsosensitazers for therapy. This review has an impact in the WP2, in which sono-responsive materials have been synthesized and mill be tested in different models within the consortium.
- (patent application): Device for monitoring the growth of a three-dimensional cell cluster and method of its manufacture (Filing date: 22.07.2024 Priority Number: 102024000016873). The tasks developed in the TheraTools project have provided the development of innovative devices to monitor cell clusters, which might impact the development of cellular models to screen drugs. The successful implementation of these devices might have an impact on 3R guides of the use of animal models.