Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10-12, 08028 Barcelona Spain.
CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Guipúzcoa, Spain.
Sci Robot. 2021 Mar 17;6(52). doi: 10.1126/scirobotics.abd2823.
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 I on gold nanoparticles or F-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.
酶驱动的纳米马达在生物医学应用中是一项令人兴奋的技术，因为它们能够利用内源性燃料在生物环境中导航。然而，对它们的集体行为的研究有限，以及在体内跟踪酶纳米马达的演示，阻碍了它们向临床转化的进展。在这里，我们报告了脲酶驱动的纳米马达的群体行为及其使用正电子发射断层扫描（PET）的体内跟踪。为此，使用了含有脲酶酶和金纳米粒子的介孔硅纳米粒子作为纳米马达。为了对它们进行成像，纳米马达用金纳米粒子上的 I 或用 F 标记的假基团对脲酶进行放射性标记。体外实验表明，纳米马达增强了流体混合和集体迁移，与非活性纳米马达相比，它们具有更高的能力在微制造的幻影中穿越复杂的路径。在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，以及 PET 适合定量跟踪体内纳米马达。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，即使有新鲜尿液进入，也观察到均匀的分布。相比之下，使用无动力纳米马达（即无燃料或无脲酶）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储器中的对流和混合。主动的集体动力学，加上医学成像跟踪，构成了生物医学纳米机器人领域的一个关键里程碑和前进的一步，为它们在治疗应用中的应用铺平了道路。
