Phase I/II trial of NBTXR3 activated by SBRT in patients with hepatocellular carcinoma or liver metastasis

Pracht, Marc; Chajon, É.; Rolland, Y.; Baere, T. de; Nguyen, F.; Bronowicki, J.-P.; Vendrely, V.; Cunha, A. Sá; Baumann, Anne-Sophie; Croisé-Laurent, V.; Rio, E.; Said, Patricia; Sourd, Samuel Le; Gustin, P.; Perret, Christophe; Peiffert, D.; Deutsch, Éric

doi:10.1093/annonc/mdz247.082

Cited by 4 publications

(6 citation statements)

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“…[228][229][230][231] For example, hafnium oxide nanoparticles in NBTXR3® have been utilized in the treatment of sarcoma in clinical practice. [232] Clinical trials of NBTXR3 have demonstrated its outstanding antitumor efficacy against soft tissue sarcoma, [233][234][235] head and neck cancer, [236] and prostate cancer. [237] However, some patients experienced grade 3 AEs (Adverse Events) such as renal toxicity, neurotoxicity, and injection-site pain, which may be attributed either to the radiotherapy (RT) itself or to associated events.…”

Section: Enzyme Woacc Npsmentioning

confidence: 99%

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

Xiao,

Zhao,

Sun

et al. 2023

Small Methods

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Radiotherapy (RT) has been a classical therapeutic method of cancer for several decades. It attracts tremendous attention for the precise and efficient treatment of local tumors with stimuli‐responsive nanomaterials, which enhance RT. However, there are few systematic reviews summarizing the newly emerging stimuli‐responsive mechanisms and strategies used for tumor radio‐sensitization. Hence, this review provides a comprehensive overview of recently reported studies on stimuli‐responsive nanomaterials for radio‐sensitization. It includes four different approaches for sensitized RT, namely endogenous response, exogenous response, dual stimuli‐response, and multi stimuli‐response. Endogenous response involves various stimuli such as pH, hypoxia, GSH, and reactive oxygen species (ROS), and enzymes. On the other hand, exogenous response encompasses X‐ray, light, and ultrasound. Dual stimuli‐response combines pH/enzyme, pH/ultrasound, and ROS/light. Lastly, multi stimuli‐response involves the combination of pH/ROS/GSH and X‐ray/ROS/GSH. By elaborating on these responsive mechanisms and applying them to clinical RT diagnosis and treatment, these methods can enhance radiosensitive efficiency and minimize damage to surrounding normal tissues. Finally, this review discusses the additional challenges and perspectives related to stimuli‐responsive nanomaterials for tumor radio‐sensitization.

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Section: Enzyme Woacc Npsmentioning

confidence: 99%

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

Xiao,

Zhao,

Sun

et al. 2023

Small Methods

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“…[26][27][28] Currently, hafnium oxide nanoparticles (NPs) based formulation is under clinical trials for different types of cancers showing its potential to be used as a potent nanomedicine component. [29,30] Further, to achieve the controlled delivery of desired drugs, both synthetic and natural polymers have been employed in the literature. [14,31] Here, natural polymers are a good choice of materials because of their inherent biocompatibility and biodegradability.…”

Section: Doi: 101002/adtp202300165mentioning

confidence: 99%

Functionalized Chitosan Decorated Hafnium Oxide@Gold Core–Shell Nanoparticles for Multimodal Cancer Therapy

Gupta,

Sood,

Bhardwaj

et al. 2023

Advanced Therapeutics

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Herein, we describe the fabrication of chitosan stabilized multifunctional hafnium oxide@gold core‐shell nanoparticles (HAT NPs) (≈12 nm). The developed nanoparticulate system offers multimodal action by providing stimuli responsive anticancer drug delivery along with imparting radiosensitization to cancer cells, thereby protecting surrounding normal tissues from damage. HAT NPs exhibit good capability of loading doxorubicin (DOX), an anticancer drug with ≈ 87% encapsulation efficiency. DOX loaded HAT NPs are able to release ≈ 91% DOX under GSH reducing conditions that is a representative of the cancer cell microenvironment. The cytotoxicity of the developed DOX loaded HAT NPs was tested against breast cancer cells (MDA‐MB‐231), showing higher cytotoxicity as compared to free DOX. Additionally, the ability of HAT NPs to generate ROS activity upon irradiation by gamma radiations (0.5 & 5 Gy) was also analysed in cancer cells to demonstrate the ability of synthesized system as a potent candidate to present radiosensitization. Further, in vivo biodistribution studies was executed to understand the tissue specific retention of HAT NPs for their future utility in targeted cancer treatment applications.This article is protected by copyright. All rights reserved

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“…Encouraged by the success of NBTXR3® for sarcoma treatment in the clinic, [27,28] which is composed of hafnium oxide nanoparticles, an increasing number of hafnium-based nanoparticles have been developed for preclinical applications. [29,30] Considering the excellent energy deposit and relative biocompatibility of hafnium ions (Hf 4+ ), [31] it was chosen to mix with 2nitroimidazole (2-nIm), [32] an X-ray responsive donor of NO, to construct nanoscale coordination polymers and then modified with lipid bilayers containing poly(ethylene glycol) (PEG) (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

X‐ray‐Induced Release of Nitric Oxide from Hafnium‐Based Nanoradiosensitizers for Enhanced Radio‐Immunotherapy

Liu

Zhu

et al. 2023

Advanced Materials

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Radiotherapy (RT) is an extensively used strategy for cancer treatment, but its therapeutic effect is usually limited by the abnormal tumor microenvironment (TME) and it lacks the ability to control tumor metastases. In this work, a nanoscale coordination polymer, Hf-nIm@PEG (HNP), is prepared by the coordination of hafnium ions (Hf 4+ ) with 2-nitroimidazole (2-nIm), and then modified with lipid bilayers containing poly(ethylene glycol) (PEG). Under low-dose X-ray irradiation, on the one hand, Hf 4+ with high computed tomography signal enhancement ability can deposit radiation energy to induce DNA damage, and on the other hand, NO can be persistently released from 2-nIm, which can not only directly react with the radical DNA to prevent the repair of damaged DNA but also relieves the hypoxic immunosuppressive TME to sensitize radiotherapy. Additionally, NO can also react with superoxide ions to generate reactive nitrogen species (RNS) to induce cell apoptosis. More interestingly, it is discovered that Hf 4+ can effectively activate the cyclic-di-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to promote the immune responses induced by radiotherapy. Thus, this work presents a simple but multifunctional nanoscale coordination polymer to deposit radiation energy, trigger the release of NO, modulate the TME, activate the cGAS-STING pathway, and finally realize synergistic radio-immunotherapy.

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Phase I/II trial of NBTXR3 activated by SBRT in patients with hepatocellular carcinoma or liver metastasis

Cited by 4 publications

References 0 publications

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

Functionalized Chitosan Decorated Hafnium Oxide@Gold Core–Shell Nanoparticles for Multimodal Cancer Therapy

X‐ray‐Induced Release of Nitric Oxide from Hafnium‐Based Nanoradiosensitizers for Enhanced Radio‐Immunotherapy

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