Enzymes play a crucial role in many biological processes which require harnessing and converting free chemical energy into kinetic forces in order to accomplish tasks. Enzymes are considered to be ...molecular machines, not only because of their capability of energy conversion in biological systems but also because enzymatic catalysis can result in enhanced diffusion of enzymes at a molecular level. Enlightened by nature’s design of biological machinery, researchers have investigated various types of synthetic micro/nanomachines by using enzymatic reactions to achieve self-propulsion of micro/nanoarchitectures. Yet, the mechanism of motion is still under debate in current literature. Versatile proof-of-concept applications of these enzyme-powered micro/nanodevices have been recently demonstrated. In this review, we focus on discussing enzymes not only as stochastic swimmers but also as nanoengines to power self-propelled synthetic motors. We present an overview on different enzyme-powered micro/nanomachines, the current debate on their motion mechanism, methods to provide motion and speed control, and an outlook of the future potentials of this multidisciplinary field.
Cancer is one of the main causes of death around the world, lacking efficient clinical treatments that generally present severe side effects. In recent years, various nanosystems have been explored ...to specifically target tumor tissues, enhancing the efficacy of cancer treatment and minimizing the side effects. In particular, bladder cancer is the ninth most common cancer worldwide and presents a high survival rate but serious recurrence levels, demanding an improvement in the existent therapies. Here, we present urease-powered nanomotors based on mesoporous silica nanoparticles that contain both polyethylene glycol and anti-FGFR3 antibody on their outer surface to target bladder cancer cells in the form of 3D spheroids. The autonomous motion is promoted by urea, which acts as fuel and is inherently present at high concentrations in the bladder. Antibody-modified nanomotors were able to swim in both simulated and real urine, showing a substrate-dependent enhanced diffusion. The internalization efficiency of the antibody-modified nanomotors into the spheroids in the presence of urea was significantly higher compared with antibody-modified passive particles or bare nanomotors. Furthermore, targeted nanomotors resulted in a higher suppression of spheroid proliferation compared with bare nanomotors, which could arise from the local ammonia production and the therapeutic effect of anti-FGFR3. These results hold significant potential for the development of improved targeted cancer therapy and diagnostics using biocompatible nanomotors.
The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nanomotors holds enormous potential in a number of applications in the biomedical field. Herein, we ...report the preparation of mesoporous silica nanoparticles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules (Ru(bpy)3Cl2 (bpy = 2,2′-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both Ru(bpy)3Cl2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to “sense” the environment and deliver the payload on demand in response to predefined stimuli.
We report lipase‐based nanomotors that are capable of enhanced Brownian motion over long periods of time in triglyceride solution and of degrading triglyceride droplets that mimic “blood lipids”. We ...achieved about 40 min of enhanced diffusion of lipase‐modified mesoporous silica nanoparticles (MSNPs) through a biocatalytic reaction between lipase and its corresponding water‐soluble oil substrate (triacetin) as fuel, which resulted in an enhanced diffusion coefficient (ca. 50 % increase) at low triacetin concentration (<10 mm). Lipase not only serves as the power engine but also as a highly efficient cleaner for the triglyceride droplets (e.g., tributyrin) in PBS solution, which could yield potential biomedical applications, for example, for dealing with diseases related to the accumulation of triglycerides, or for environmental remediation, for example, for the degradation of oil spills.
Lipase‐based nanomotors that are capable of enhanced Brownian motion over long periods of time in triglyceride solution and of degrading triglyceride droplets have been synthesized. The biocatalytic reaction between lipase and its water‐soluble oil substrate triacetin as fuel led to about 40 min of enhanced diffusion of lipase‐modified mesoporous silica nanoparticles.
The use of enzyme catalysis to power micro‐ and nanomotors exploiting biocompatible fuels has opened new ventures for biomedical applications such as the active transport and delivery of specific ...drugs to the site of interest. Here, urease‐powered nanomotors (nanobots) for doxorubicin (Dox) anticancer drug loading, release, and efficient delivery to cells are presented. These mesoporous silica‐based core–shell nanobots are able to self‐propel in ionic media, as confirmed by optical tracking and dynamic light scattering analysis. A four‐fold increase in drug release is achieved by nanobots after 6 h compared to their passive counterparts. Furthermore, the use of Dox‐loaded nanobots presents an enhanced anticancer efficiency toward HeLa cells, which arises from a synergistic effect of the enhanced drug release and the ammonia produced at high concentrations of urea substrate. A higher content of Dox inside HeLa cells is detected after 1, 4, 6, and 24 h incubation with active nanobots compared to passive Dox‐loaded nanoparticles. The improvement in drug delivery efficiency achieved by enzyme‐powered nanobots may hold potential toward their use in future biomedical applications such as the substrate‐triggered release of drugs in target locations.
The capability of enzyme‐propelled nanomotors to enhance drug delivery is investigated in this study. Urease‐powered nanomotors show active motion in ionic media and significantly improve the release of doxorubicin in the presence of urea. The synergy between the resulting catalytic products and the enhanced drug delivery results in higher cytotoxic effect toward HeLa cells.
Developing self‐powered nanomotors made of biocompatible and functional components is of paramount importance in future biomedical applications. Herein, the functional features of LipoBots (LBs) ...composed of a liposomal carrier containing urease enzymes for propulsion, including their protective properties against acidic conditions and their on‐demand triggered activation, are reported. Given the functional nature of liposomes, enzymes can be either encapsulated or coated on the surface of the vesicles. The influence of the location of urease on motion dynamics is first studied, finding that the surface‐urease LBs undergo self‐propulsion whereas the encapsulated‐urease LBs do not. However, adding a percolating agent present in the bile salts to the encapsulated‐urease LBs triggers active motion. Moreover, it is found that when both types of nanomotors are exposed to a medium of similar pH found in the stomach, the surface‐urease LBs lose activity and motion capabilities, while the encapsulated‐urease LBs retain activity and mobility. The results for the protection enzyme activity through encapsulation within liposomes and in situ triggering of the motion of LBs upon exposure to bile salts may open new avenues for the use of liposome‐based nanomotors in drug delivery, for example, in the gastrointestinal tract, where bile salts are naturally present in the intestine.
Enzyme‐powered nanomotors are designed by attaching or encapsulating urease onto or into liposomes, which act as a nanomotor chassis and protective shell for urease. The propulsion of nanomotors encapsulating urease is triggered by a percolating agent present in the bile salts. Moreover, enzyme encapsulation on the inner liposomal compartment allows preservation of functionality when the nanomotors are exposed to harsh conditions.
In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), ...dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular dichroism spectroscopy indicate that the self-assembly process is driven by stacking interactions of the aromatic groups. The naphthalene groups of the naproxen moieties are highly organized in the fibers through chiral stacking. Rheological experiments demonstrated that the most hydrophobic peptide (containing C-terminal ΔPhe) formed more elastic gels at lower critical gelation concentrations. This gel revealed irreversible breakup, while the C-terminal ΔAbu and ΔAla gels, although less elastic, exhibited structural recovery and partial healing of the elastic properties. A potential antitumor thieno3,2-bpyridine derivative was incorporated (noncovalently) into the gel formed by the hydrogelator containing C-terminal ΔPhe residue. Fluorescence and Förster resonance energy transfer measurements indicate that the drug is located in a hydrophobic environment, near/associated with the peptide fibers, establishing this type of hydrogel as a good drug-nanocarrier candidate.
The motion of self-propelled tubular micro- and nanojets has so far been achieved by bubble propulsion, e.g., O2 bubbles formed by catalytic decomposition of H2O2, which renders future biomedical ...applications inviable. An alternative self-propulsion mechanism for tubular engines on the nanometer scale is still missing. Here, we report the fabrication and characterization of bubble-free propelled tubular nanojets (as small as 220 nm diameter), powered by an enzyme-triggered biocatalytic reaction using urea as fuel. We studied the translational and rotational dynamics of the nanojets as functions of the length and location of the enzymes. Introducing tracer nanoparticles into the system, we demonstrated the presence of an internal flow that extends into the external fluid via the cavity opening, leading to the self-propulsion. One-dimensional nanosize, longitudinal self-propulsion, and biocompatibility make the tubular nanojets promising for future biomedical applications.
The low efficacy of current conventional treatments for bacterial infections increases mortality rates worldwide. To alleviate this global health problem, we propose drug-free enzyme-based nanomotors ...for the treatment of bacterial urinary-tract infections. We develop nanomotors consisting of mesoporous silica nanoparticles (MSNPs) that were functionalized with either urease (U-MSNPs), lysozyme (L-MSNPs), or urease and lysozyme (M-MSNPs), and use them against nonpathogenic planktonic Escherichia coli. U-MSNPs exhibited the highest bactericidal activity due to biocatalysis of urea into NaHCO3 and NH3, which also propels U-MSNPs. In addition, U-MSNPs in concentrations above 200 μg/mL were capable of successfully reducing 60% of the biofilm biomass of a uropathogenic E. coli strain. This study thus provides a proof-of-concept, demonstrating that enzyme-based nanomotors are capable of fighting infectious diseases. This approach could potentially be extended to other kinds of diseases by selecting appropriate biomolecules.
We report lipase‐based nanomotors that are capable of enhanced Brownian motion over long periods of time in triglyceride solution and of degrading triglyceride droplets that mimic “blood lipids”. We ...achieved about 40 min of enhanced diffusion of lipase‐modified mesoporous silica nanoparticles (MSNPs) through a biocatalytic reaction between lipase and its corresponding water‐soluble oil substrate (triacetin) as fuel, which resulted in an enhanced diffusion coefficient (ca. 50 % increase) at low triacetin concentration (<10 mm). Lipase not only serves as the power engine but also as a highly efficient cleaner for the triglyceride droplets (e.g., tributyrin) in PBS solution, which could yield potential biomedical applications, for example, for dealing with diseases related to the accumulation of triglycerides, or for environmental remediation, for example, for the degradation of oil spills.
Lipase‐basierte Nanomotoren zeigen in Triglycerid‐Lösung über lange Zeiträume verstärkte Brownsche Bewegung und bauen Triglycerid‐Tröpfchen ab. Die biokatalytische Reaktion zwischen der Lipase und ihrem wasserlöslichen Ölsubstrat Triacetin als Kraftstoff führt zu einer erhöhten Diffusion der Lipase‐modifizierten mesoporösen Siliciumdioxid‐Nanopartikel für ca. 40 min.
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