Publications

Over the past decades, the development of nanoparticles (NPs) to increase the efficiency of clinical treatments has been subject of intense research. Yet, most NPs have been reported to possess low efficacy as their actuation is hindered by biological barriers. For instance, synovial fluid (SF) present in the joints is mainly composed of hyaluronic acid (HA). These viscous media pose a challenge for many applications in nanomedicine, as passive NPs tend to become trapped in complex networks, which reduces their ability to reach the target location. This problem can be addressed by using active NPs (nanomotors, NMs) that are self-propelled by enzymatic reactions, although the development of enzyme-powered NMs, capable of navigating these viscous environments, remains a considerable challenge. Here, the synergistic effects of two NMs troops, namely hyaluronidase NMs (HyaNMs, Troop 1) and urease NMs (UrNMs, Troop 2) are demonstrated. Troop 1 interacts with the SF by reducing its viscosity, thus allowing Troop 2 to swim more easily through the SF. Through their collective motion, Troop 2 increases the diffusion of macromolecules. These results pave the way for more widespread use of enzyme-powered NMs, e.g., for treating joint injuries and improving therapeutic effectiveness compared with traditional methods. The conceptual idea of the novel approach using hyaluronidase NMs (HyaNMs) to interact with and reduce the viscosity of the synovial fluid (SF) and urease NMs (UrNMs) for a more efficient transport of therapeutic agents in joints.image

JTD Keywords: Biological barrier, Clinical research, Clinical treatments, Collective motion, Collective motion,nanomotors,nanorobots,swarming,viscous medi, Collective motions, Complex networks, Enzymatic reaction, Enzymes, Hyaluronic acid, Hyaluronic-acid,ph,viscoelasticity,adsorption,barriers,behavior,ureas, Macromolecules, Medical nanotechnology, Nano robots, Nanomotors, Nanorobots, Swarming, Synovial fluid, Target location, Viscous media, Viscous medium

Targeted drug delivery depends on the ability of nanocarriers to reach the target site, which requires the penetration of different biological barriers. Penetration is usually low and slow because of passive diffusion and steric hindrance. Nanomotors (NMs) have been suggested as the next generation of nanocarriers in drug delivery due to their autonomous motion and associated mixing hydrodynamics, especially when acting collectively as a swarm. Here, we explore the concept of enzyme-powered NMs designed as such that they can exert disruptive mechanical forces upon laser irradiation. The urease-powered motion and swarm behavior improve translational movement compared to passive diffusion of state-of-the-art nanocarriers, while optically triggered vapor nanobubbles can destroy biological barriers and reduce steric hindrance. We show that these motors, named Swarm 1, collectively displace through a microchannel blocked with type 1 collagen protein fibers (barrier model), accumulate onto the fibers, and disrupt them completely upon laser irradiation. We evaluate the disruption of the microenvironment induced by these NMs (Swarm 1) by quantifying the efficiency by which a second type of fluorescent NMs (Swarm 2) can move through the cleared microchannel and be taken up by HeLa cells at the other side of the channel. Experiments showed that the delivery efficiency of Swarm 2 NMs in a clean path was increased 12-fold in the presence of urea as fuel compared to when no fuel was added. When the path was blocked with the collagen fibers, delivery efficiency dropped considerably and only depicted a 10-fold enhancement after pretreatment of the collagen-filled channel with Swarm 1 NMs and laser irradiation. The synergistic effect of active motion (chemically propelled) and mechanical disruption (light-triggered nanobubbles) of a biological barrier represents a clear advantage for the improvement of therapies which currently fail due to inadequate passage of drug delivery carriers through biological barriers.

JTD Keywords: drug delivery, enzyme catalysis, nanoparticles, swarming, vapor nanobubbles, Drug delivery, Enzyme catalysis, Nanomotors, Nanoparticles, Swarming, Vapor nanobubbles