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Urease-powered nanobots for radionuclide bladder cancer therapy
Nature Nanotechnology ( IF 38.3 ) Pub Date : 2024-01-15 , DOI: 10.1038/s41565-023-01577-y
Cristina Simó , Meritxell Serra-Casablancas , Ana C. Hortelao , Valerio Di Carlo , Sandra Guallar-Garrido , Sandra Plaza-García , Rosa Maria Rabanal , Pedro Ramos-Cabrer , Balbino Yagüe , Laura Aguado , Lídia Bardia , Sébastien Tosi , Vanessa Gómez-Vallejo , Abraham Martín , Tania Patiño , Esther Julián , Julien Colombelli , Jordi Llop , Samuel Sánchez

Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.



中文翻译:

用于放射性核素膀胱癌治疗的脲酶驱动纳米机器人

通过膀胱内给药的膀胱癌治疗取得了合理的生存率,但治疗效果较低。为了解决后者,人们提出了自驱动纳米颗粒或纳米机器人,与传统药物或被动纳米颗粒相比,它们利用了它们在尿液中增强的扩散和混合能力。然而,纳米机器人治疗膀胱癌的转化能力尚未得到充分探索。在这里,我们在膀胱癌原位小鼠模型中测试了放射性标记的介孔二氧化硅基脲酶驱动的纳米机器人。体内和离体结果表明,纳米机器人在肿瘤部位的积累增强,体内正电子发射断层扫描显示增加了八倍。基于透明膀胱的偏振依赖性散射光片显微镜的无标记光学对比证实了纳米机器人离体肿瘤的渗透。用膀胱内注射放射性碘化纳米机器人进行放射性核素治疗,对荷瘤小鼠进行治疗,可使肿瘤尺寸缩小约 90%,使纳米机器人成为膀胱癌治疗的有效递送纳米系统。

更新日期:2024-01-15
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