Radiotherapy | Nano Publications

2017 – AACR Abstract – NBTXR3 combination with cisplatin in vivo and in vitro

Congress Abstracts, In Vitro, In Vitro in Vivo NBTXR3, In Vivo

Combination of NBTXR3 and cisplatin has been evaluated in vitro and in vivo. No specific toxicity was observed for the cells exposed only to NBTXR3. For the combined treatment, a marked and enhanced cell destruction when compared to the single agent. In vivo, NBTXR3 combined with low dose of cisplatin delayed tumor growth when compared to single agent CDDP in combination with RT. NBTXR3 is intended to be injected in the tumors. Spilling in the circulation may occur during product administration or, as expected, during tumor destruction, leading to steady trapping of NPs in the reticulo-endothelial system (liver and spleen). Clinically, it is unknown whether patients, previously treated with NPs, may show toxic signs when NPs are exposed (activation) to diagnosis imaging (computed tomography(CT)) of the liver.

2017 – AACR Abstract – NBTXR3 anti-tumor efficacy in vivo

Congress Abstracts, In Vitro in Vivo NBTXR3, In Vivo

NBTXR3 has been evaluated in numerous in vivo models. The antitumor efficacy was systematically enhanced in terms of tumor growth delay for animals treated with NBTXR3 and exposed to radiotherapy when compared to radiotherapy alone. In this abstract the transferability of the treatment with NBTXR3 from one type of cancer to the other is described. NBTXR3 is intended to be injected in the tumors. Spilling in the circulation may occur during product administration or, as expected, during tumor destruction, leading to steady trapping of NPs in the reticulo-endothelial system (liver and spleen). Clinically, it is unknown whether patients, previously treated with NPs, may show toxic signs when NPs are exposed (activation) to diagnosis imaging (computed tomography(CT)) of the liver.

2017 – A phase 1 trial of NBTXR3 nanoparticles activated by IMRT in the treatment of advanced-stage head and neck carcinoma

Clinical Data NBTXR3, Congress Abstracts, Head & Neck

Functionalized hafnium oxide nanoparticles (NBTXR3) have been developed as selective radioenhancers, which may represent a breakthrough approach for the local treatment of solid tumors. The high electron density of the nanoparticles, when exposed to radiotherapy (RT), allow the absorption/deposition of a high radiation dose within the tumor cells, to physically kill the cells and possibly improve outcome.

2017 – Specific adaptive immune pattern induced by NBTXR3 exposed to radiation therapy in soft tissue sarcoma (STS) patients

Clinical Data NBTXR3, Congress Abstracts, STS

NBTXR3 are functionalized hafnium oxide nanoparticles, undergoing seven clinical trials for enhancing radiation therapy (RT). The high electron density of the nanoparticles, when exposed to radiotherapy (NBTXR3 + RT), allow absorption/deposition of a high radiation dose within the cancer cells to physically kill the cells, and possibly improve outcome. Besides, NBTXR3 + RT has shown subsequent ability to enhance immunogenic cell death and immune response in preclinics. We hypothesized that NBTXR3 + RT could trigger an enhanced immune response when compared to RT in patients with STS.

2016 – SITC Abstract – NBTXR3 for in situ cancer vaccination

Congress Abstracts, In Vitro in Vivo NBTXR3, In Vivo

NBTXR3 exposed to irradiation enhanced cancer cells destruction and immunogenic cell death compared to irradiation alone, suggesting a strong potential for transforming tumor into an effective in situ vaccine. This may contribute to transform “cold” tumor into “hot” tumor and effectively be combined with most of the immunotherapeutic agents across oncology. NBTXR3 is intended to be injected in the tumors. Spilling in the circulation may occur during product administration or, as expected, during tumor destruction, leading to steady trapping of NPs in the reticulo-endothelial system (liver and spleen). Clinically, it is unknown whether patients, previously treated with NPs, may show toxic signs when NPs are exposed (activation) to diagnosis imaging (computed tomography(CT)) of the liver.

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

Clinical Data NBTXR3, NO-RIGHTS, Publications, STS

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).

2015 – Clinical Sciences and Drug Discovery Abstract – Use of metals as nano-sized radiation enhancers – Pottier et al.

Congress Abstracts, Miscellaneous

Since the discovery of cisplatin about 40 years ago, the design of innovative metal-based anticancer drugs is a growing area of research. Metal elements offer specific characteristics due to their intrinsic properties and could be used in relation to their final state: a metal complex, a radionuclide, a metal-based nanoparticle product. Transition metal coordination complexes interact with cell molecular targets, affecting biochemical functions resulting in cancer cell destruction. Radionuclides are another way to use metals as anticancer therapy. The metal nucleus of the unstable radionuclide becomes stable by emitting energy. The biological effect in different tissues is obtained by the absorption of this energy from the radiation emitted by the radionuclide, the principal target generally agreed for ionizing radiations being DNA. A new area of clinical research is now emerging using the same experimental metal elements, but in a radically different manner: metals and metal oxides used as crystalline nanosized radiation enhancers particles. The use of metals as a high electron density material tailored at the nanoscale when exposed to radiotherapy is a unique approach that can allow entry to the cell and make feasible the absorption/deposition of a high-energy dose within the tumor cell (on/off activity). Therefore, high electron density metal or metal oxide nanoparticles may bring well known physical mode of action, that of radiotherapy, within malignant cells and achieve the paradigm of local cancer treatment.

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

Miscellaneous, NO-RIGHTS, Publications

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.

2011 – ECCO Abstract – NBTXR3 as promising cancer therapy – Magiorella et al.

Congress Abstracts, In Vitro, In Vitro in Vivo NBTXR3

We created and developed NBTXR3 nanoparticles with a crystalline hafnium oxide core which provide high electron density structure and inert behavior in biological media. NBTXR3 nanoparticles’ characteristics, size, charge and shape, allow for efficient interaction with biological entities, cell membrane binding and cellular uptake. The nanoparticles were shown to form clusters at the subcellular level in tumor models. Of most importance, we show NBTXR3 intratumor bioavailability with dispersion of nanoparticles in the three dimensions and persistence within the tumor structure, supporting the use of NBTXR3 as effective antitumor therapeutic agent.

2010 – Concept of NBTXR3 – Borghi et al.

Miscellaneous, NO-RIGHTS, Publications

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.