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2017 – A new opportunity for nanomedicines – Paolini et al.

Nanomedicines are mainly used as drug delivery systems; here we evaluate a new application - to inhibit a drug's metabolism thereby enhancing its effective dose. Micelles containing the natural furanocoumarin 6′,7′ dihydroxybergamottin (DHB), a known CYP450 inhibitor, were developed to transiently block hepatic CYP450-mediated drug metabolism and increase the bioavailability of the oncology drug docetaxel.

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2016 – Phase I data NBTXR3 Soft Tissue Sarcoma – Bonvalot et al.

This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS). Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks).

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2015 – Metals as radio-enhancers in oncology – Pottier et al.

Radio-enhancers, metal-based nanosized agents, could play a key role in oncology. They may unlock the potential of radiotherapy by enhancing the radiation dose deposit within tumors when the ionizing radiation source is ‘on’, while exhibiting chemically inert behavior in cellular and subcellular systems when the radiation beam is ‘off’. Important decision points support the development of these new type of therapeutic agents originated from nanotechnology. Here, we discuss from an industry perspective, the interest of developing radio-enhancer agents to improve tumor control, the relevance of nanotechnology to achieve adequate therapeutic attributes, and present some considerations for their development in oncology.

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2015 – The future of nanosized radiation enhancers – Pottier et al.

Radiotherapy has a universal and predictable mode of action, that is, a physical mode of action consisting of the deposit of a dose of energy in tissues. Tumour cell damage is proportional to the energy dose. However, the main limitation of radiotherapy is the lack of spatial control of the deposition of energy, that is, it penetrates the healthy tissues, damages them and renders unfeasible delivery of an efficient energy dose when tumours are close to important anatomical structures. True nanosized radiation enhancers may represent a disruptive approach to broaden the therapeutic window of radiation therapy.

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2014 – Metals as Nanosized Radioenhancers – Pottier et al.

Since the discovery of cisplatin about 40 years ago, the design of innovative metal-based anticancer drugs is a growing area of research. Transition metal coordination complexes offer potential advantages over the more common organic-based drugs, including a wide range of coordination number and geometries, accessible redox states, tunability of the thermodynamics and kinetics of ligand substitution, as well as a wide structural diversity. Metal-based substances interact with cell molecular targets, affecting biochemical functions resulting in cancer cell destruction. Radionuclides are another way to use metals as anticancer therapy.

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2014 – NBTXR3 concept and dose enhancement – Marill et al.

Hafnium oxide, NBTXR3 nanoparticles were designed for high dose energy deposition within cancer cells when exposed to ionizing radiation. The purpose of this study was to assess the possibility of predicting the in vitro the biological effect of NBTXR3 nanoparticles when exposed to ionizing radiation. Cellular uptake of NBTXR3 nanoparticles was assessed in a panel of human cancer cell lines (radioresistant and radiosensitive) by transmission electron microscopy. The radioenhancement of NBTXR3 nanoparticles was measured by the clonogenic survival assay.

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2012 – Efficacy of NBTXR3 in vitro and in vivo – Maggiorella et al.

There is considerable interest in approaches that could improve the therapeutic window of radiotherapy. In this study, hafnium oxide nanoparticles were designed that concentrate in tumor cells to achieve intracellular highenergy dose deposit. Materials & methods: Conventional methods were used, implemented in different ways, to explore interactions of these high-atomicnumber nanoparticles and ionizing radiation with biological systems.

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2010 – Concept of NBTXR3 – Borghi et al.

La nanotechnologie permet une gestion et un assemblage de matériaux sans précédent dans l’histoire des produits utilisés en santé humaine. Cette révolution est apportée par la possibilité d’utiliser de nouveaux mécanismes thérapeutiques et de dissocier les différentes fonctions de la substance médicamenteuse (distribution, effet thérapeutique…), ce qui était jusqu’ici impossible avec les médicaments classiques.

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2010 – Silica Nanoparticles – Simon et al.

Protoporphyrin IX (Pp IX) silica nanoparticles, developed for effective use in photodynamic therapy (PDT), were explored in in vitro and in vivo models with the ambition to improve knowledge on the role of biological factors in the photodamage. Pp IX silica nanoparticles are found efficient at temperature with extreme metabolic downregulation, which suggest a high proportion of passive internalization. For the first time, clearance of silica nanoparticles on tumor cells is established. Cell viability assessment in six tumor cell lines is reported.

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