Project: NanoSonoChemotherapy for Diffuse Intrinsic Pontine Glioma

Acronym	NSC4DIPG (Reference Number: EURONANOMED2017-123)
Duration	01/08/2018
Project Topic	Diffuse intrinsic pontine gliomas (DIPG) are highly aggressive brain tumors that typically affect children at an age of 6-10, and for which no curative treatments are currently available. DIPG are diffusely located within the brainstem, which controls vital functions, making surgery impossible and radiotherapy very difficult. Moreover, both classical and targeted chemotherapeutic drugs fail in DIPG because of the presence of a largely intact blood-brain barrier (BBB). The BBB is arguably the most formidable barrier for drug delivery to the brain and to brain tumors as it prevents drugs and drug delivery systems from reaching the pathological site. We here aim to use sonoporation, which relies on the combination of ultrasound and microbubbles, to create a temporal window during which nanomedicine formulations can be shuttled across the BBB. Several clinically relevant nanocarriers will be used, including 10 nm linear polymers, 40 nm engineered protein capsules, 70 nm polymeric micelles, 100 nm PEGylated liposomes and 150 nm PACA-based polymeric nanoparticles. These established carrier materials will be loaded with optimized combinations of classical (anthracyclines) and molecularly targeted (histone deacetylase inhibitors) anticancer agents, and their release profiles will be tailored to allow for sustained and synergistic multi-drug activity within sonoporated DIPG lesions. Patient-derived xenografts will be used to study the kinetics of BBB opening, the target site accumulation of the developed nanomedicines, and the efficacy of NanoSonoChemotherapy. Optimized sonoporation protocols will be established, to maximize the temporal and spatial specificity of BBB opening and nanomedicine-mediated drug delivery. All nanomedicine formulations, sonoporation protocols and treatment regimens will be extensively characterized with regard to safety, ensuring that all components of this radically new treatment paradigm can be readily translated to the clinic in the near future.
Network	EuroNanoMed III
Call	Joint Transnational Call for Proposals (2017) for “European Innovative Research & Technological Development Projects in Nanomedicine”

Project partner

Number	Name	Role	Country
1	Uniklinik RWTH Aachen	Coordinator	Germany
2	NEUWAY Pharma GmbH	Partner	Germany
3	Vrije Universiteit Medisch Centrum	Partner	Netherlands
4	Universitair Medisch Centrum Utrecht	Partner	Netherlands
5	SINTEF Materials and Chemistry	Partner	Norway