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用于增强肿瘤氧合和磁共振成像的可注射生物相容性沸石纳米晶体

Injectable Biocompatible Zeolite Nanocrystals for Enhanced Tumor Oxygenation and MRI Imaging.

作者信息

Amedlous Abdallah, Hélaine Charly, Dalena Francesco, Anfray Clément, Ménard Thomas, Blanchard Isis, Toutain Jérôme, Valable Samuel, Mintova Svetlana

机构信息

Université de Caen Normandie, ENSICAEN, CNRS, LCS, 14000 Caen, France.

ISTCT UMR6030, Université de Caen Normandie, CNRS, Normandie Université, GIP CYCERON, F-14000 Caen, France.

出版信息

ACS Appl Mater Interfaces. 2025 Feb 5;17(5):8003-8016. doi: 10.1021/acsami.4c20383. Epub 2025 Jan 24.

Abstract

Tumor hypoxia significantly limits the effectiveness of radiotherapy, as oxygen is crucial for producing cancer-killing reactive oxygen species. To address this, we synthesized nanosized faujasite (PBS-Na-FAU) zeolite crystals using clinical-grade phosphate-buffered saline (PBS) as the solvent, ensuring preserved crystallinity, microporous volume, and colloidal stability. The zeolite nanocrystals showed enhanced safety profiles and , and studies showed no apparent toxicity to animals. They demonstrated a high oxygen capacity with a release rate of 2.68 mg/L under hypoxic conditions. The introduction of gadolinium (Gd) into the zeolite nanocrystals by ion exchange, replacing three monovalent cations (Na and K), led to an increased oxygen capacity of the sample. In situ Fourier transform infrared (FTIR) study revealed that Gd-containing zeolite (PBS-Gd-FAU) adsorbed ∼23% more oxygen at 20 kPa compared to the as-synthesized sample (PBS-Na-FAU). magnetic resonance imaging (MRI) demonstrated targeted oxygen delivery and release within brain tumors, revealing 14.91 and 17.10% differences in cerebral blood volume (CBV) between tumor and contralateral brain tissue after 15 and 20 min, respectively, compared to the control. 1 maps at 7 T indicated a relaxation rate of 9.254 mM·s for PBS-Gd-FAU, twice that of commercial Gd-chelates. These findings highlight the potential of Gd-containing zeolite nanocrystals synthesized in PBS as a biocompatible platform for enhancing tumor oxygenation in anticancer therapy, with significant clinical translation potential.

摘要

肿瘤缺氧显著限制了放射治疗的效果,因为氧气对于产生抗癌活性氧至关重要。为了解决这个问题,我们使用临床级磷酸盐缓冲盐水(PBS)作为溶剂合成了纳米级八面沸石(PBS-Na-FAU)沸石晶体,确保了结晶度、微孔体积和胶体稳定性得以保留。沸石纳米晶体显示出更高的安全性,并且研究表明对动物没有明显毒性。它们在缺氧条件下表现出高氧容量,释放速率为2.68 mg/L。通过离子交换将钆(Gd)引入沸石纳米晶体中,取代三个单价阳离子(Na和K),导致样品的氧容量增加。原位傅里叶变换红外(FTIR)研究表明,与合成后的样品(PBS-Na-FAU)相比,含Gd的沸石(PBS-Gd-FAU)在20 kPa下吸附的氧气多约23%。磁共振成像(MRI)证明了在脑肿瘤内靶向输氧和释氧,与对照相比,分别在15分钟和20分钟后,肿瘤与对侧脑组织之间的脑血容量(CBV)差异为14.91%和17.10%。7 T下的1图谱表明PBS-Gd-FAU的弛豫率为9.254 mM·s,是商业Gd螯合物的两倍。这些发现突出了在PBS中合成的含Gd沸石纳米晶体作为一种生物相容性平台在抗癌治疗中增强肿瘤氧合的潜力,具有显著的临床转化潜力。

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