Bienzymatic Spiky Janus Nanomotors Powered by Histamine

Abstract

As an important inflammatory mediator, histamine can be produced by many immune cells (mast cells, neutrophils, dendritic cells, platelets, etc.) and modulates a variety of immune events. Developing enzymatic micro/ nanomotors from the perspective of immunometabolism is required but still lacking. In this work, we functionalized the histamine-metabolizing enzyme onto the Janus Au/mSiO 2 nanoparticles. Powered by the tandem catalytic decomposition of histamine initiated by a surface-modified diamine oxidase, this nanomotor system exhibits an enhanced diffusive motion with increasing histamine concentration. At a concentration of histamine (500 mM), the motor speed reaches 9.25 � 1.71 μm.s À 1 , which is 2.3 times that of Brownian motion, and the corresponding diffusion coefficient is enhanced by 137%. This novel enzymatic nanomotor system not only expands the physiologic enzyme library for biomedical micro/nanomotors but also provides new ideas for the immune therapy of diseases targeting histamine.

Enzyme-powered micro- and nano-motors: key parameters for an application-oriented design

“…51,52 All these combinations rely on the transference of electrons through the motor structure to generate a selfelectrophoretic mechanism that produces motion, but there are others that just exploit the tandem reactions to trigger selfdiffusiophoresis such as glucose oxidase-horseradish peroxidase, 94 sarcosine oxidase and catalase, 41 or diamine oxidase and catalase. 101 A similar designed has been reported by combining enzymatic engines with inorganic catalysts such as xanthin oxidase-Pt and glutamate oxidase-Pt. 50 There is even one example of a whole enzymatic network (Fig.…”

“…5B and C) appealing for biomedical applications, with special interest around 200 nm diameter for transport in the bloodstream. Such enzymatic motors are made of different materials like polymeric structures, 13,23,37,40 liposomal vesicles, [117][118][119] metalbased structures 42,62,101,113 and silica-based particles, 71,97,99,104,109 mainly applied as active drug delivery systems and chemotactic nanotools towards biologically relevant environments. Their small size promotes a proper navigation in complex media, and although only a few enzymes t on the structure, it is enough to produce active motion.…”

“…Metals like Au and Fe 3 O 4 have been also combined with silica to take advantage of the same magnetic and photo-reactive properties, 92–95 to attach isotopes for visualization, 96 to create an asymmetric incorporation of enzymes, 97–101 or to synthesize an organoclay chassis. 102 There are even examples of polymers combined with both silica and metals such as (1) MnFe 2 O 4 added as a layer in the combination of silica with poly( l -lysine), poly(methacrylic acid) and poly(ethylene glycol) (SiO 2 -PLL-PMA-MnFe 2 O 4 -PEG) 103 or (2) Au nanoparticles added between layers of poly(ethylene glycol), poly(acrylic acid) and mesoporous silica (PEG-Au-PAA- m SiO 2 ), 104 to offer magnetic guidance and to induce an asymmetric chassis structure, respectively.…”

“…88 Hence, it is combined with polymers to additionally confer these properties, for example silica with polystyrene (PS-SiO 2 ) 89 , poly(sodium styrene sulfonate) (PSS-SiO 2 ), 57 PNIPAM (PNIPAM-SiO 2 ) 90 or other combinations of increasing complexity like silica with polydopamine, poly(L-lysine) and poly(ethylene glycol) (SiO 2 -PDA-PLL-PEG) 91 . Metals like Au and Fe 3 O 4 have been also combined with silica to take advantage of the same magnetic and photoreactive properties, [92][93][94][95] to attach isotopes for visualization, 96 to create an asymmetric incorporation of enzymes, [97][98][99][100][101] or to synthesize an organoclay chassis. 102 There are even examples of polymers combined with both silica and metals such as (1) MnFe 2 O 4 added as a layer in the combination of silica with poly(L-lysine), poly(methacrylic acid) and poly(ethylene glycol) (SiO 2 -PLL-PMA-MnFe 2 O 4 -PEG) 103 or (2) Au nanoparticles added between layers of poly(ethylene glycol), poly(acrylic acid) and mesoporous silica (PEG-Au-PAA-mSiO 2 ), 104 to offer magnetic guidance and to induce an asymmetric chassis structure, respectively.…”

“…However, it has been argued that the asymmetry of product release is needed for selfpropulsion to take place, 128 which is normally provided by adding fabrication steps to break the complete symmetry of spherical structures. For years, this has been solved by attaching enzymatic engines only on one side of the motor creating Janus structures through different methods such as synthesizing motors via a microuidics system, 28,29 growing different materials on each side of the particle, 95,101,109 directly attaching two spherical particles together (each of them being a side of the Janus structure), 97 or modifying one side of the particle aer synthesis using the interfacial energy difference, 104 through a sputtering process, 44,69,70,92,99 by spin-coating, 110 by using a Pickering emulsion, 68,77,91,94,103 and modifying the spheres while attached on a bigger sphere 67 or while magnetically attracted to a surface. 43,62 There are examples of spherical shapes where instead of forcing asymmetry, active motion was produced by fully covering with enzymes the surface of rigid spheres, 13,14,16,31,34,57,60,65,85 porous spheres [71][72][73][74][75][76]78,80,96,125 and hollow spheres, 21,…”