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, 9 (1), 117-23

Artificial Micromotors in the Mouse's Stomach: A Step Toward in Vivo Use of Synthetic Motors

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Artificial Micromotors in the Mouse's Stomach: A Step Toward in Vivo Use of Synthetic Motors

Wei Gao et al. ACS Nano.

Abstract

Artificial micromotors, operating on locally supplied fuels and performing complex tasks, offer great potential for diverse biomedical applications, including autonomous delivery and release of therapeutic payloads and cell manipulation. Various types of synthetic motors, utilizing different propulsion mechanisms, have been fabricated to operate in biological matrices. However, the performance of these man-made motors has been tested exclusively under in vitro conditions (outside the body); their behavior and functionalities in an in vivo environment (inside the body) remain unknown. Herein, we report an in vivo study of artificial micromotors in a living organism using a mouse model. Such in vivo evaluation examines the distribution, retention, cargo delivery, and acute toxicity profile of synthetic motors in mouse stomach via oral administration. Using zinc-based micromotors as a model, we demonstrate that the acid-driven propulsion in the stomach effectively enhances the binding and retention of the motors as well as of cargo payloads on the stomach wall. The body of the motors gradually dissolves in the gastric acid, autonomously releasing their carried payloads, leaving nothing toxic behind. This work is anticipated to significantly advance the emerging field of nano/micromotors and to open the door to in vivo evaluation and clinical applications of these synthetic motors.

Keywords: cargo delivery; in vivo; nanomotors; toxicity; zinc.

Figures

Figure 1
Figure 1
Preparation and characterization of PEDOT/Zn micromotors. (a) Schematic of the in vivo propulsion and tissue penetration of the zinc-based micromotors in mouse stomach. (b) Preparation of PEDOT/Zn micromotors using polycarbonate membrane templates: (I) deposition of the PEDOT microtube, (II) deposition of the inner zinc layer, and (III) dissolution of the membrane and release of the micromotors. (c) Scanning electron microscopy (SEM) image (left) of the PEDOT/Zn micromotors and the corresponding energy-dispersive X-ray spectroscopy (EDX) data (right) of elemental Zn in the micromotors. Scale bar, 5 μm. (d) Time lapse images (1 s intervals, I–IV) of the propulsion of PEDOT/Zn micromotors in gastric acid under physiological temperature (37 °C). Scale bar, 20 μm.
Figure 2
Figure 2
Tissue retention of PEDOT/Zn micromotors. (a–d) Microscopic images illustrate the retained micromotors on the stomach tissues collected at (a) 2 h, (b) 6 h, and (c) 12 h post-oral administration of PEDOT/Zn micromotors and (d) 2 h post-oral administration of PEDOT/Pt micromotors (serving as a negative control). Scale bars, 100 μm. (e) Enumeration of the density of PEDOT/Zn and PEDOT/Pt micromotors retained on the stomach tissues at the different times after the administration.
Figure 3
Figure 3
In vivo cargo delivery. (a) SEM image of a AuNP-loaded PEDOT/Zn micromotor (left) and EDX analysis illustrating the presence of Zn (middle) and Au (right) within the motor. Scale bar, 5 μm. (b) Inductively coupled plasma-mass spectrometry (ICP-MS) analysis of the amount of gold retained on the stomach tissues. The AuNP-loaded PEDOT/Zn micromotors or AuNPs were administered orally to the mice, and the stomach tissues were collected 2 h post the administration.
Figure 4
Figure 4
Toxicity evaluation of PEDOT/Zn micromotors. The mouse stomach was treated with PBS buffer (a, b), PEDOT/Zn micromotor (c, d), AuNPs (e, f), and AuNP-loaded PEDOT/Zn micromotors (g, h). At 6 h post-treatment, the mice were sacrificed and sections of the mouse stomach were processed as described in the Methods section and stained with H&E assay (a, c, e, and g) or TUNEL assay (b, d, f, and h). Scale bars, 250 μm.

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