Enzyme-Powered Hollow Mesoporous Janus Nanomotors

Abstract

The development of synthetic nanomotors for technological applications in particular for life science and nanomedicine is a key focus of current basic research. However, it has been challenging to make active nanosystems based on biocompatible materials consuming nontoxic fuels for providing self-propulsion. Here, we fabricate self-propelled Janus nanomotors based on hollow mesoporous silica nanoparticles (HMSNPs), which are powered by biocatalytic reactions of three different enzymes: catalase, urease, and glucose oxidase (GOx). The active motion is characterized by a mean-square displacement (MSD) analysis of optical video recordings and confirmed by dynamic light scattering (DLS) measurements. We found that the apparent diffusion coefficient was enhanced by up to 83%. In addition, using optical tweezers, we directly measured a holding force of 64 ± 16 fN, which was necessary to counteract the effective self-propulsion force generated by a single nanomotor. The successful demonstration of biocompatible enzyme-powered active nanomotors using biologically benign fuels has a great potential for future biomedical applications.

Micro- and nano-motors: the New Generation of Drug Carriers

“…Besides, the velocities of these motors have been very low, in the order of a few micrometers per second on average. So far, numerous efforts have been made to improve speed [31], directionality [32], and to enhance the enzymatic motor activity by using, for example, electroactive polymers to encapsulate higher amounts of enzyme [33], or hollow mesoporous structures to increase the reactive surface area [34]. Alternatively, materials that decompose in a slightly acidic environment, such as zinc, manganese or calcium carbonate, have also been employed to fabricate micro-/nano-motors that can be operated in environments like the stomach or the vicinity of cancer cells, both exhibiting a pH below 7 [35,36].…”

“…The oxygen bubbles were expelled from one side of the carbon nanotube, inducing its forward motion [61]. From then on, different synthetic structures such as porous Janus nanomotors, [62] rolled-up microtubes [31] and stomatocytes [63,64] have been used to immobilize or carry enzymes which can react with the surrounding environment, leading to self-propulsion of the microand nano-motors via enhanced diffusion or bubble formation [65]. Recently, Sanchez's group reported the use of enzymatic mesoporous nanomotors which move in urease-based media to carry and deliver DOX onto cancer cells in vitro, showing that the drug-loaded nanomotors were more effective in killing cancer cells when they were in presence of urea, compared to passive carriers, due to the motor kinetics and the ammonia production by the catalytic decomposition of urea ( Figure 1D & Table 1) [51].…”

Enzyme-coated Janus nanoparticles that selectively bind cell receptors as a function of the concentration of glucose

“…It has been proposed that enzyme-coated Janus nanoparticles can move by means of a diffusiophoretic mechanism. 6,7 The velocity of these Janus particles is related to the concentration of the enzyme substrate. It is also well established that biomolecular interactions can be mechanically disrupted, for example, by pulling biomolecules apart with an atomic force microscope or with optical tweezers.…”

“…The particle design could be easily adapted to respond to the concentration of other metabolites such as urea or hydrogen peroxide by simply changing GOx for urease or catalase, respectively. 6,7 This concept is promising for developing a new family of particles that selectively establish interactions with cells as a function of the concentration of different metabolites present in the cell microenvironment.…”

“…This size was chosen because it is similar to the size of previously reported enzymepowered nanomotors. 7,14 Nanoparticle motion was studied with dynamic light scattering (DLS), which is a validated technique for studying changes in the diffusion coefficient of enzyme-covered Janus nanoparticles. 7 The diffusion coefficient of the nanoparticles in the absence of glucose is 0.36 ± 0.01 μm 2 s −1 .…”