A phase I/II trial of hafnium oxide nanoparticles activated by radiotherapy in hepatocellular carcinoma and liver metastasis

Dual-Stimuli-Responsive Multifunctional Gd2Hf2O7 Nanoparticles for MRI-Guided Combined Chemo-/Photothermal-/Radiotherapy of Resistant Tumors

“…First of all, Gd 2 Hf 2 O 7 NPs were prepared by a modified anhydrous solvothermal approach using PAA as the dispersant, which ensures them good water solubility and ultrasmall size. The design is based on the fact that Gd 2 Hf 2 O 7 NPs not only provide MRI signal enhancement but also possess good ROS generation ability under X-ray radiation. ,, Afterward, a thin layer of PDA was modified on the Gd 2 Hf 2 O 7 NPs through controlling the reaction time. The PDA on the surface of NPs can load chemotherapeutic drugs and release them under the stimulus of the tumor microenvironment or NIR laser .…”

“…Apart from the good photothermal effects and dual-stimuli-responsive drug release ability of Gd 2 Hf 2 O 7 @PDA@PEG-Pt-RGD NPs, the high atomic number elements (Gd and Hf) in Gd 2 Hf 2 O 7 @PDA@PEG-Pt-RGD NPs provide the potential augmentation of radiotherapy effect. , The performance of ROS generation in vitro , induced by Gd 2 Hf 2 O 7 @PDA@PEG-Pt-RGD NPs exposed to X-ray radiation, was estimated to characterize the radiotherapy effect. Hoechst dye was used to stain cell nucleus, and the ROS generation in drug-resistant A549R cells was detected by the DCFH-DA green fluorescence probe.…”

“…Hafnium dioxide (HfO 2 ) is regarded as an outstanding potential radiosensitizer for clinical trials, 30 and the phase II/III studies of HfO 2 -based NPs (NBTXR3) in soft tissue sarcoma of patients are successful [NCT02379845]. 31,32 Moreover, HfO 2 is regarded as a superb host matrix and can be utilized for rare-earth element dopants, which offers opportunities to synthesize advanced nanomedicine with multimodal properties. 33−35 Based on the radioenhancement ability of lanthanide doping in the HfO 2 matrix, we choose Gd as the dopant to endow the Gd 2 Hf 2 O 7 nanoplatform radiotherapy effect, r 1 relaxivity, and excellent biosafety.…”

“…In the present work, an innovative type of multifunctional NPs was prepared and explored for the operating principle of the MRI-guided chemo-, photothermal-, and radiotherapy against cisplatin-resistant tumors. Hafnium dioxide (HfO 2 ) is regarded as an outstanding potential radiosensitizer for clinical trials, and the phase II/III studies of HfO 2 -based NPs (NBTXR3) in soft tissue sarcoma of patients are successful [NCT02379845]. , Moreover, HfO 2 is regarded as a superb host matrix and can be utilized for rare-earth element dopants, which offers opportunities to synthesize advanced nanomedicine with multimodal properties. − Based on the radioenhancement ability of lanthanide doping in the HfO 2 matrix, we choose Gd as the dopant to endow the Gd 2 Hf 2 O 7 nanoplatform radiotherapy effect, r 1 relaxivity, and excellent biosafety. , Furthermore, after modification of polydopamine (PDA), a kind of PTT agents, the nanoplatform can be used to transport cisplatin and control release precisely with laser irradiation and low pH in tumor microenvironments. , PEG and RGD on the surface endow this nanoplatform with feasible biostability and tumor-targeting ability. Upon intravenous (iv) injection of such a new nanomedicine platform, the superior therapeutic outcome in tumor growth inhibition was obtained through the combined three kinds of therapy methods.…”

Harnessing Hafnium‐Based Nanomaterials for Cancer Diagnosis and Therapy

“…These characteristics indicated that HfO 2 NPs have low toxicity, consequently reducing their potential biological security concerns. [26,27] NBTXR3, mainly composed of HfO 2 modified by negatively charged polymer comprising phosphate groups, provided by NANOBIOTIX Company, has entered the clinical trial II/III phase for many kinds of tumor therapy, [28,29] and the achievement of European market approval (CE marking) for NBTXR3 (brand-name: Hensify) in the treatment of locally advanced soft tissue sarcoma was concluded in 2019. Currently, clinical studies on synergistic CHT and IT based on HfO 2 -mediated radiosensitization effects are also underway.…”