One-dimensional micro/nanomotors for biomedicine: delivery, sensing and surgery

Abstract

The rapid development of artificial micro/nanomachines brings promising strategies to overcome challenges in biomedicine, including delivery, sensing and surgery. One-dimensional (1D) micro/nanomotors are one of the most attractive micro/nanomachines due to their high specific surface area, powerful impetus and weak rotation diffusion. In this review, different propulsion mechanisms and motion control strategies of 1D micro/nanomotors are summarized, and recent efforts towards their fabrication methods and biomedical applications are discussed. We envision the multidisciplinary research efforts in the field of 1D micro/nanomotors will pave their way to practical applications in bioimaging and biomedicine.

Keywords: biomedicine; micromotor; nanomotor; one-dimensional.

Figure 1. Schematic illustration of chemical propulsion mechanisms used in one-dimensional micro/nanomotors. (A) Scheme of Pt/Au nanowire motors propelled by a self-electrophoretic mechanism in H₂O₂ solution. Reprinted with permission from Wang et al. Copyright (2006) American Chemical Society. (B) Scheme of tubular micromotors propelled by ejecting O₂ bubbles in H₂O₂ solution. Reprinted with permission from Manjare et al. Copyright (2013) American Chemical Society. (C) Scheme of PANI/Zn tubular microtube propelled by recoiling H₂ bubbles in aqueous acid. Reproduced with permission from Gao et al. Copyright (2012) American Chemical Society. (D) SiO₂/urease tubular nanomotor propelled by the diffusion flux of reaction products. Reprinted with permission from Ma et al. Copyright (2016) American Chemical Society. PANI: polyaniline.

Figure 2. Representative examples of external field propulsion mechanisms of one-dimensional micro/nanomotors. (A) Au nanowire (Au NW) propelled and aligned by AC and DC electric fields in patterned microelectrodes. Reprinted with permission from Fan et al. Copyright (2008) American Institute of Physics. (B) Multilayered tubular micromotors decorated with gold nanoparticles propelled by NIR light. Reprinted with permission from Wu et al. Copyright (2016) John Wiley and Sons. (C) Au/Ru bimetallic nanowire with concave and convex ends propelled by ultrasound as well as its trajectories of axial directional motion and in-plane rotation. Reproduced with permission from Wang et al. Copyright (2012) American Chemical Society. (D) Ni/Ag/Au flexible nanowire propelled by rotational magnetic field. Reproduced with permission from Gao et al. Copyright (2010) American Chemical Society. AC: alternating current; DC: direct current; f: frequency; GND: Ground; NIR: near infrared; R1: Ni segment; R2: Au segment; V: magnetic swimming direction.

Figure 3. Motion control of one-dimensional micro/nanomotors via external fields. (A) Directional motion and reversing of tubular micromotors remotely guided by a magnetic field. Reproduced with permission from Zhao et al. Copyright (2012) American Chemical Society. (B) Two dimensions and three dimensions movement of Pt/Au bimetallic nanowire motors manipulated by three-dimensional orthogonal microelectrodes. Reprinted with permission from Guo et al. Copyright (2018) American Chemical Society. AC: alternating current; hv: light radiation.

Figure 4. Architectural effects on the motive behaviour of one-dimensional micro/nanomotors. (A) The rotation speed could be adjusted by the distribution ratio of Pt/Au on the Au/Pt/Au nanorods coated with a Au/Cr layer on one face. Reproduced with permission from Qian et al. Copyright (2007) American Chemical Society. (B) Enzymes on inner or exterior surface of nanotubes enhanced the longitudinal translational and rotational diffusions, respectively. Reproduced with permission from Ma et al. Copyright (2016) American Chemical Society. (C) A copper nanowire with a rachet on one end was able to rotate whereas a symmetric nanowire was not. Reproduced with permission from Liu and Sen. Copyright (2011) American Chemical Society. (D) Tuning the velocity of tubular micromotors by adjusting the semi-cone angle. Reproduced with permission from Gallino et al. Copyright (2018) John Wiley and Sons.

Figure 5. Fabrication of one-dimensional micro/nanomotors. (A) Anodic alumina oxide membrane template-assisted electrochemical deposition for the preparation of metallic nanowires. Reproduced with permission from Wang and Pumera and Wang et al. Copyright (2015) & (2006) American Chemical Society. (B) Rolled-up technique for the preparation of tubular micromotors. Reproduced with permission from Mei et al. and Soloveo et al. Copyright (2008) & (2009) & (2010) John Wiley and Sons. (C) Combination of layer-by-layer assembly, microcontact printing and rolled-up technique for the fabrication of tubular micromotors. Reproduced with permission from Hu et al. Copyright (2018) John Wiley and Sons. (D) Electroplating with carbon materials for the preparation of tubular micromotors. Reproduced with permission Maria-Hormigos et al. Copyright (2016) American Chemical Society. (E) Bottom-up assembly for tubular nanomotors. Reproduced with permission from Peng et al. Copyright (2018) Royal Society of Chemistry. (F) Combination of block polymer lithography and atomic layer deposition for the fabrication of tubular nanomotors. Reproduced with permission from Li et al. Copyright (2017) John Wiley and Sons. CN: carbon nanotube; NIR: near infrared; PC: polycarbonate; PEM: polyelectrolyte multilayer.

Figure 6. Organic small molecule drug delivery using one-dimensional micro/nanomotors. (A) Ni/(Au₅₀/Ag₅₀ alloy)/Ni/Pt nanowire motors enabled the pick up, transport and release of Dox-loaded PLGA particles at predetermined positions. Reproduced with permission from Kagan et al. Copyright (2010) John Wiley and Sons. (B) Tubular micromotors encapsulating Dox could move to targeted cancer cells under magnetic guidance and subsequently be triggered to release Dox by a near infrared laser. Reproduced with permission from Wu et al. Copyright (2015) American Chemical Society. PLGA: poly(lactic-co-glycolic acid).

Figure 7. Rapid intracellular delivery of proteins (A) and RNAs (B) with ultrasound-propelled gold nanowire (AuNW) motors. Reproduced with permission from Esteban-Fernández de Ávila et al. and Díez et al. Copyright (2017) & (2016) American Chemical Society. CASP-3: caspase-3; US: ultrasound.

Figure 8. Tuning distribution of drugs in gastrointestinal organs by varying the thickness of a pH-responsive polymer coating on a Mg-based tubular micromotor. Reproduced with permission from Li et al.⁹³ Copyright (2016) American Chemical Society. EMgMs: enteric Mg micromotors; PEDOT: poly(3,4-ethylenedioxythiophene).

Figure 9. Sensing using one-dimensional micro/nanomotors. (A) Scheme of tubular micromotors tailored with antibody for cancer biomarker detection (e.g. CEA). Reproduced with permission from Yu et al. Copyright (2014) American Chemical Society. (B) Scheme of tubular micromotors for targeted DNA detection through the detachment of active materials (catalase). Reproduced with permission from Fu et al. Copyright (2017) Royal Society of Chemistry. Ab2-GMA: secondary-antibody-modified glycidyl methacrylate microspheres; AFP: alpha fetoprotein; CEA: carcinoembryonic antigen.

Figure 10. One-dimensional nanomotors for single cell sensing. (A) Ag/Ni/Ag three-segment nanorods coated with Ag nanoparticles used to analyse the chemicals of a single cell. Reproduced with permission from Xu et al. Copyright (2013) John Wiley and Sons. (B) Ultrasound-propelled nanorod modified with fluorescent dye-labelled ssDNA for miRNA detection of a single cell. Reproduced with permission from Esteban-Fernández de Ávila et al. Copyright (2015) Royal Society of Chemistry. US: ultrasound.

Figure 11. One-dimensional micro/nanomotors for surgery. (A) Tubular micromotors propelled by acoustic droplet vaporization for cellular tissue ablation. Reproduced with permission from Kagan et al. Copyright (2012) John Wiley and Sons. (B) Implantable magnetic tubular micromotors for wireless ophthalmologic surgery. Reproduced with permission from Chatzipirpiridis et al. Copyright (2014) John Wiley and Sons. (C) Ultrasound-propelled gold nanowires loaded with a Cas9/sgRNA complex for rapid and efficient gene knockout. Reproduced with permission from Hansen-Bruhn et al.¹⁰⁴ Copyright (2018) John Wiley and Sons. AuNW: gold nanowire; Cys: cysteine; GFP: green fluorescent protein; GSH: glutathione; MPA: 3-mercaptopropionic acid; sgRNA: single guide RNA; US: ultrasound.