HypoCyclo · Multifunctional Polymeric Cyclodextrin Nanocarriers As Novel Triple-Negative Breast Cancer Treatment: A Versatile Photo-Chemotherapy Bypassing Hypoxic Conditions
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-09-01 → 2023-08-31
- EU contribution
- €257,210
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Multifunctional Polymeric Cyclodextrin Nanocarriers As Novel Triple-Negative Breast Cancer Treatment: A Versatile Photo-Chemotherapy Bypassing Hypoxic Conditions
Among all breast cancers affecting female population worldwide, 20% is represented by Triple Negative Breast Cancer (TNBC), an aggressive subtype with very limited therapeutic options and poor survival rates. There is a continuous search for new therapeutic approaches that can overcome the shortcomings of the actually used therapies, mainly surgery and chemotherapy. Seeking for innovation in TNBC therapies, the HypoCyclo project focuses the optimal combination of chemotherapy and photodynamic therapy (PDT). PDT, a less known therapeutic approach, consists in the administration of a molecule absorbing red light, known as "photosensitizer" which produces reactive oxygen species (ROS), mainly singlet oxygen, upon irradiation with red light in the presence of oxygen. ROS can start a cascade of biological processes eventually killing cancer cells. PDT has become a feasible option thanks to the technological advances in lasers and fiber-optics allowing interstitial and intra-operative light delivery for the treatment of solid tumours, including breast cancers. The presence of oxygen is necessary for both chemotherapy and PDT to be effective. However, breast cancers often suffer from low oxygen levels, called hypoxia, limiting efficacy of the chosen therapies and therefore, and new systems that are able to release oxygen at the cancer site are currently investigated. The objective of the project is the combination of chemotherapy with photodynamic therapy in optimized conditions for the effective treatment of TNBC also in hypoxic conditions. We plan to prepare new polymeric nanoparticles able to load cancer drugs together with a photosensitizer for PDT as well as an oxygen releasing agent (ORA). The goal of the project is also to keep the synthetic protocols simple, low-cost and green, in order to facilitate industrial application of the nanoparticles that perform best.
Data: CORDIS, © European Union
Project objective
Among all breast cancers (BC) affecting female population worldwide, 20% is represented by Triple Negative Breast Cancer (TNBC), an aggressive subtype with very limited therapeutic options and poor survival. Seeking for innovative TNBC therapies, HypoCyclo aims at the optimal combination of chemotherapy and photodynamic therapy (PDT). We envisage novel, tailored cyclodextrin (CyD)-based polymeric nanoparticles (NPs) able to load “known” therapeutic agents and decorated with a photosensitizer as well as an Oxygen-Releasing Agent. HypoCyclo focuses on the very effective drug paclitaxel (PCX) presenting several treatment problems like water insolubility. Biocompatible, novel CyD polymers are expected to solubilize and encapsulate through non-covalent binding the drug of choice in order to implement PCX chemotherapy with PDT, through the decoration with a PS able to generate antitumor reactive oxygen species (ROS) in situ. Indeed, PDT has become a very challenging yet feasible option thanks to the technological advances in lasers and fiber-optics allowing interstitial and intra-operative light delivery for the treatment of solid tumours, including BC. Finally, as hypoxia in BC tissue compromises standard chemotherapy and PDT, we will tailor our NPs with an ORA able to release oxygen in cells, enabling an alternative ROS source. The PCX loaded NPs will be completely characterized and tested in 2D and 3D TNBC models. Our goal is to keep the synthetic protocols simple, low-cost and green to facilitate industrial upgrade of the loaded multimodal NPs endowed with improved in vitro efficacy. Two partners, the SME Cyclolab and UNIBO, both already collaborating with the supervisor, will give the necessary support in mixed-CyD polymer synthesis and in the biological assays, respectively, guaranteeing a successful outcome. The project foresees a demanding training program for ER that will help him to become an independent researcher with a complete profile.
Original text from CORDIS.
Participants
- CONSIGLIO NAZIONALE DELLE RICERCHE · RomaCoordinatorItaly
Links
Data: CORDIS, © European Union