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Swarming behavior and in vivo monitoring of enzymatic nanomotors within the bladder
Science Robotics ( IF 26.1 ) Pub Date : 2021-03-17 , DOI: 10.1126/scirobotics.abd2823
Ana C Hortelao 1 , Cristina Simó 2 , Maria Guix 1 , Sandra Guallar-Garrido 3 , Esther Julián 3 , Diana Vilela 1 , Luka Rejc 2 , Pedro Ramos-Cabrer 2, 4 , Unai Cossío 2 , Vanessa Gómez-Vallejo 2 , Tania Patiño 1, 5 , Jordi Llop 2 , Samuel Sánchez 1, 6
Affiliation  

Enzyme-powered nanomotors are an exciting technology for biomedical applications due to their ability to navigate within biological environments using endogenous fuels. However, limited studies into their collective behavior and demonstrations of tracking enzyme nanomotors in vivo have hindered progress toward their clinical translation. Here, we report the swarming behavior of urease-powered nanomotors and its tracking using positron emission tomography (PET), both in vitro and in vivo. For that, mesoporous silica nanoparticles containing urease enzymes and gold nanoparticles were used as nanomotors. To image them, nanomotors were radiolabeled with either 124I on gold nanoparticles or 18F-labeled prosthetic group to urease. In vitro experiments showed enhanced fluid mixing and collective migration of nanomotors, demonstrating higher capability to swim across complex paths inside microfabricated phantoms, compared with inactive nanomotors. In vivo intravenous administration in mice confirmed their biocompatibility at the administered dose and the suitability of PET to quantitatively track nanomotors in vivo. Furthermore, nanomotors were administered directly into the bladder of mice by intravesical injection. When injected with the fuel, urea, a homogeneous distribution was observed even after the entrance of fresh urine. By contrast, control experiments using nonmotile nanomotors (i.e., without fuel or without urease) resulted in sustained phase separation, indicating that the nanomotors’ self-propulsion promotes convection and mixing in living reservoirs. Active collective dynamics, together with the medical imaging tracking, constitute a key milestone and a step forward in the field of biomedical nanorobotics, paving the way toward their use in theranostic applications.



中文翻译:

膀胱内酶促纳米马达的蜂群行为和体内监测

酶驱动的纳米马达是一项令人兴奋的生物医学应用技术,因为它们能够使用内源性燃料在生物环境中导航。然而,对它们的集体行为和体内跟踪酶纳米马达的演示的有限研究阻碍了它们临床转化的进展。在这里,我们报告了脲酶驱动的纳米马达的蜂拥行为及其在体外和体内使用正电子发射断层扫描 (PET) 进行的跟踪。为此,使用含有脲酶和金纳米颗粒的介孔二氧化硅纳米颗粒作为纳米马达。为了对它们成像,纳米马达在金纳米粒子上用124 I 或18F-标记的假体组为脲酶。体外实验表明,与非活性纳米马达相比,纳米马达的流体混合和集体迁移增强,表明在微制造的幻影中游过复杂路径的能力更高。小鼠体内静脉给药证实了它们在给药剂量下的生物相容性和 PET 在体内定量跟踪纳米马达的适用性。此外,纳米马达通过膀胱内注射直接注入小鼠的膀胱。当注入燃料尿素时,即使在新鲜尿液进入后也观察到均匀分布。相比之下,使用非运动性纳米马达(即,没有燃料或没有脲酶)的对照实验导致持续的相分离,表明纳米马达的自推进促进了活水库中的对流和混合。主动集体动力学与医学成像跟踪一起构成了生物医学纳米机器人领域的一个关键里程碑和向前迈出的一步,为它们在治疗诊断应用中的应用铺平了道路。

更新日期:2021-03-18
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