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Multifunctional Polymeric Cyclodextrin Nanocarriers As Novel Triple-Negative Breast Cancer Treatment: A Versatile Photo-Chemotherapy Bypassing Hypoxic Conditions

Descrizione del progetto

Terapia a base di nanoparticelle per il cancro al seno

Il carcinoma mammario triplo negativo rappresenta quasi il 20 % di tutti i casi di cancro al seno ed è caratterizzato da aggressività e scarsa sopravvivenza. Poiché la maggior parte delle terapie fallisce, il progetto HypoCyclo, finanziato dall’UE, è alla ricerca di alternative innovative. Gli scienziati propongono di offrire una combinazione ottimale di chemioterapia e terapia fotodinamica mediante nanoparticelle. Oltre a farmaci efficaci quali il paclitaxel, le nanoparticelle trasporteranno fotosensibilizzanti e agenti che rilasciano ossigeno per contrastare l’ipossia tumorale e migliorare l’efficacia del trattamento. L’idea è quella di combinare la somministrazione di nanoparticelle con laser e fibre ottiche che agevolano l’erogazione di luce interstiziale e intraoperatoria. I ricercatori prevedono un protocollo di sintesi di nanoparticelle semplice per garantire una produzione a basso costo e quindi su larga scala.

Obiettivo

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.

Coordinatore

CONSIGLIO NAZIONALE DELLE RICERCHE
Contribution nette de l'UE
€ 257 209,92
Indirizzo
PIAZZALE ALDO MORO 7
00185 Roma
Italia

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Regione
Centro (IT) Lazio Roma
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 257 209,92