Publications

Biological barriers present a significant obstacle to treatment, especially when drugs are administered locally to increase their concentrations at the target site while minimizing unintended off-target effects. Among these barriers, mucus presents a challenge, as it serves as a protective layer in the respiratory, urogenital, and gastrointestinal tracts. Its role is to shield the underlying epithelial cells from pathogens and toxic compounds but also impedes the efficient delivery of drugs. Despite the exploration of mucolytic agents to improve drug delivery, overcoming this protective barrier remains a significant hurdle. In our study, we investigate an alternative approach involving the use of catalase-powered nanobots. We use an in vitro model that simulates intestinal mucus secretion to demonstrate the dual functionality of our nanobots. This includes their ability to disrupt mucus, which we confirmed through in vitro and ex vivo validation, as well as their self-propulsion to overcome the mucus barrier, resulting in a 60-fold increase compared with passive nanoparticles. Therefore, our findings highlight the potential utility of catalase-powered nanobots as carriers for therapeutic agents since they could enhance drug delivery efficiency by penetrating the mucus barrier.

JTD Keywords: Biological barrier, Biological barriers, Drug-delivery, Growth, Hydrogen-peroxide, Muci, Mucus, Nanobots, Nanomedicine, Nanomotors, Transport

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