POLAR STAR · Polymeric cyclodextrin-based nanoparticles for combination therapy of castrate-resistant prostate cancer

Polymeric cyclodextrin-based nanoparticles for combination therapy of castrate-resistant prostate cancer

With about 375 000 deaths worldwide in 2020, PC is the fifth leading cause of cancer-related death in the male population. Localized PC can be successfully cured by radical surgery or radiation therapy while the advanced and metastatic PC diseases are treated mainly with androgen deprivation therapy (ADT). ADT-sensitive PC often evolves into Castration Resistant Prostate Cancer (CRPC). The lack of efficacious treatments for CRPC has led to an urgent need for the development of new therapies. These will likely require personalized therapy based on combination therapy with drugs targeting different metabolisms specifically operating in CRPC. Administration of multiple therapeutics can be difficult because of unfavorable distribution in the body, rapid body clearance, limited tumor accessibility and toxicity. In this frame, nanotechnology for drug delivery can offer a series of advantages such as the possibility to load in a unique nanoparticle system high amounts of drugs as well as the combination of more than one therapeutic agent. POLAR STAR aims at the implementation of combination therapy to treat CRPC. Our strategy is to exploit nanotechnology to administer contemporarily different therapeutic agents that synergically act across multiple oncogenic pathways. We plan to use new polymers based on cyclodextrins (CyD) as these are already FDA approved. The Polar Star Objective is the combination of known antitumoral drugs with “less known” therapeutic agents as it may open new roads for innovation in CRPC treatment. As to “less known” therapeutics, we are interested in agents able to produce cytotoxic species upon light irradiation. The idea is to combine known drugs together with a photosensitizer (PS) which upon irradiation with red light in the presence of oxygen produces Reactive Oxygen Species starting a cascade of processes finally killing the cancer cells. To implement combination therapy we aim at the preparation of nanoparticles (NPs) of polymerized CyDs able to encapsulate both the drugs and the PS. The loaded polymeric NPs will be further studied in biological assays with the goal to assess toxicity on normal and tumor prostate cells. We plan to obtain cell proliferation profiles for the various NP formulations. We also aim at the rationalization of the biological response of 3D PC organoids after treatment with the loaded NPs. Our final goal is the preparation of different NPs that encapsulates the right amounts of drugs and photosensitizer that are ready for the application in vivo.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз