Swarming behavior and in vivo monitoring of enzymatic nanomotors within the bladder

Abstract

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.

Polymeric Micro/Nanocarriers and Motors for Cargo Transport and Phototriggered Delivery

“…The principal propulsion mechanisms are photic [285], magnetic [286], catalytic [287,288], self-electrophoretic [289], self-diffusiophoretic [290], and the Marangoni effect [291], showing the versatility of the MNs in generating motion [292]. In particular, polymeric and catalytic Janus-particle-based MNs consist of an anisotropic particle with two faces with different characteristics so as to generate a specific reaction on one side to produce the motion while performing different tasks (capturing, transporting, (bio)sensing, etc.)…”

A Practical Guide to Analyzing and Reporting the Movement of Nanoscale Swimmers

“…Both refer to the transport of colloidal particles in a self-generated chemical gradient, 31,45,172 with major differences being whether the chemically active particle is a combination of source and sink of chemicals (self-electrophoresis), or just a source (self-diffusiophoresis). The particular case of self-diffusiophoresis, which is the most commonly invoked mechanism for a chemical nanoswimmer, [59][60][61][62]66,79 can be further divided into ionic and neutral types, depending on the nature of the released chemicals. Ionic self-diffusiophoresis occurs when the released ions have different diffusivities, or have different interactions with the particle, and it weakens as the solution ionic strength increases.…”

Bioinspired urease-powered micromotor as an active oral drug delivery carrier in stomach

“…Here, we developed bioinspired urease-powered polydopamine (PDA) micromotor as a biomimetic system of Helicobacter (H) pylori for active oral drug delivery in the stomach. As reported elsewhere [ [20] , [21] , [22] , [23] ], our micromotor used urea in stomach as a bioavailable power source for the propulsion of synthetic motors. The micromotor was prepared with a PDA hollow microcapsule, which showed not only good biocompatibility and biodegradability but also muco-adhesive property [ [24] , [25] , [26] , [27] ].…”