A phase II/III trial of hafnium oxide nanoparticles activated by radiotherapy in the treatment of locally advance soft tissue sarcoma of the extremity and trunk wall

Bonvalot, S.; Rutkowski, Piotr; Thariat, Juliette; Carrère, Sébastien; Sunyach, M.P.; Saâda, Esma; Ágoston, Péter; Hong, Angela; Mervoyer, A.; Rastrelli, Marco; Péchoux, C. Le; Moreno,; Li, R; Tiangco, B.; Herráez, Antonio Casado; Gronchi, Alessandro; Mangel, László; Hohenberger, Peter; Delannes, M.; Papaï, Z.

doi:10.1093/annonc/mdy424.081

Cited by 9 publications

(8 citation statements)

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“…While a deeper mechanistic understanding of the ROS production would be of great interest, commonly used fluorescence ROS assays show strong assay interference, therefore alternative strategies are warranted. In addition, future research may also be aimed at identifying optimal routes for MXenes delivery, exploiting strategies such as intratumoral injection (similarly to what is done for hafnium dioxide nanoparticle delivery to soft tissue sarcoma tumors today 53 ), as well as encapsulation.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy Enhancement by Ti3C2Tx MXenes

Zimmermann

Gerken

Wee

et al. 2023

Preprint

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Radiotherapy is an integral part of cancer therapy. Due to the low tissue specificity of radiation, damage to tumor-surrounding healthy tissue remains a major concern. Radio-enhancers based on inorganic nanomaterials have attracted considerable attention in recent years. In addition to widely exploited metal and metal oxides nanoparticles, 2D materials may offer potential advantages due to their intrinsically high specific surface area. Here, we report on the promising radio-enhancement properties of Ti3C2Tx MXenes. We show that Ti3C2Tx MXenes are readily internalized and well-tolerated by mammalian cells. In contrast to MXenes suspended in aqueous buffers which fully oxidize within days (yielding rice-grain shaped rutile nanoparticles), MXenes internalized by cells display slower oxidation rates, in line with cell-free experiments showing slower oxidation in cell media and lysosomal buffers compared to antioxidant-devoid dispersants. The MXenes show potent radio-enhancement properties with dose enhancement factors of up to 2.5 in human soft tissue sarcoma cells and no toxicity towards healthy human fibroblasts. Benchmarking against oxidized MXenes and commercial titanium dioxide nanoparticles indicates superior radio-enhancement properties of the intact 2D titanium carbide flakes. Taken together, this work provides direct evidence for the potent radio-enhancement properties of Ti3C2Tx MXenes rendering them a promising candidate material for radiotherapy enhancement.

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Section: Discussionmentioning

confidence: 99%

Radiotherapy Enhancement by Ti3C2Tx MXenes

Zimmermann

Gerken

Wee

et al. 2023

Preprint

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“…135 The phase II/III trial showed positive results in patients with soft tissue sarcomas. 136 Studies showed that radiotherapy-activated NBTXR3 NPs were not excreted in the urine, and did not leak into the tissue surrounding the tumor, and no side effects were observed. This study showed that NP amounts >10% of the tumor volume had a beneficial response over time, and was reported to be suitable for elderly or chemotherapy intolerant patients.…”

Section: Hafnium Oxide Npsmentioning

confidence: 99%

“…In addition, hafnium oxide NPs are inert and have no toxicity to living cells, which made them promising in various clinical trials 135 . The phase II/III trial showed positive results in patients with soft tissue sarcomas 136 . Studies showed that radiotherapy‐activated NBTXR3 NPs also played an essential role in inducing an anti‐tumor immune response 134,137 .…”

Section: High‐z Np‐based Radiosensitizersmentioning

confidence: 99%

Application of nano‐radiosensitizers in combination cancer therapy

Varzandeh

Sabouri

Mansouri

et al. 2023

Bioengineering & Transla Med

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Radiosensitizers are compounds or nanostructures, which can improve the efficiency of ionizing radiation to kill cells. Radiosensitization increases the susceptibility of cancer cells to radiation‐induced killing, while simultaneously reducing the potentially damaging effect on the cellular structure and function of the surrounding healthy tissues. Therefore, radiosensitizers are therapeutic agents used to boost the effectiveness of radiation treatment. The complexity and heterogeneity of cancer, and the multifactorial nature of its pathophysiology has led to many approaches to treatment. The effectiveness of each approach has been proven to some extent, but no definitive treatment to eradicate cancer has been discovered. The current review discusses a broad range of nano‐radiosensitizers, summarizing possible combinations of radiosensitizing NPs with several other types of cancer therapy options, focusing on the benefits and drawbacks, challenges, and future prospects.

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“…[268] For radioenhancement, therapeutically effective nanomaterial concentrations in the tumor are typically rather high, and are therefore especially challenging to achieve by conventional intravenous administration. Therefore, current clinical studies (both for HfO2 (Hensify) [269] and for nanoparticle tumor hyperthermia) [270] employ intratumoral injection as a preferred route of delivery. While clinically successful (improved patient outcome), this delivery route limits the applicability of the therapy to a small subset of patients with only locally advanced and well-accessible tumors.…”

Section: Delivery Of Radioenhancersmentioning

confidence: 99%

Prospects of Nanoparticle-based Radioenhancement for Radiotherapy

Gerken

Gerdes

Pruschy

et al. 2023

Preprint

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Radiotherapy is a key pillar of solid cancer treatment. Despite high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs-at risk and subsequent normal tissue toxicities. Nanotechnology offers an attractive opportunity for increasing the efficacy and safety of cancer radiotherapy. Leveraging the freedom of design and the growing synthetic capabilities of the nanomaterial-community, a variety of engineered nanomaterials have been designed and investigated as radiosensitizers or radioenhancers. While research so far has been primarily focused on gold nanoparticles and other high atomic number materials to increase the absorption cross section of tumor tissue, recent studies are challenging the traditional concept of high-Z nanoparticle radioenhancers and highlight the importance of catalytic activity. This review provides a concise overview on the fundamental knowledge of nanoparticle radioenhancement mechanisms and their quantification. It critically discusses potential radioenhancer candidate materials and general design criteria for different radiation therapy modalities, and concludes with research priorities in order to advance the development of nanomaterials, to enhance the efficacy of radiotherapy and to increase at the same time the therapeutic window.

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A phase II/III trial of hafnium oxide nanoparticles activated by radiotherapy in the treatment of locally advance soft tissue sarcoma of the extremity and trunk wall

Cited by 9 publications

References 0 publications

Radiotherapy Enhancement by Ti3C2Tx MXenes

Radiotherapy Enhancement by Ti3C2Tx MXenes

Application of nano‐radiosensitizers in combination cancer therapy

Prospects of Nanoparticle-based Radioenhancement for Radiotherapy

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