Motion of Enzyme-Powered Nanomotors in Complex Media
[eng] In recent years, the field of NMs has experienced rapid growth in biomedical applications, largely due to their ability to navigate complex physiological environments. However, unlocking their full clinical potential requires a deeper understanding of NMs modulate with and interact with biolog...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/226617 |
| Acceso en línea: | https://hdl.handle.net/2445/226617 http://hdl.handle.net/10803/696567 |
| Access Level: | acceso embargado |
| Palabra clave: | Nanotecnologia Nanomedicina Materials nanoestructurats Biocatàlisi Nanotechnology Nanomedicine Nanostructured materials Biocatalysis |
| Sumario: | [eng] In recent years, the field of NMs has experienced rapid growth in biomedical applications, largely due to their ability to navigate complex physiological environments. However, unlocking their full clinical potential requires a deeper understanding of NMs modulate with and interact with biological interfaces. This doctoral thesis aims to address this need by focusing on the design, synthesis, and evaluation of enzyme-powered NMs capable of propelling in viscous biological environments. To this end, this PhD thesis investigates a variety of NPs platforms, ranging from inorganic and polymer-based nanocarriers, functionalized with enzymes to produce enzyme-powered NMs. These NMs are evaluated across clinically relevant scenarios, including navigation in biological barriers, tissue regeneration or drug delivery. The first part of the thesis focuses on the development of inorganic-based NMs, such as those based on MSNPs, demonstrating a dual-enzyme NMs strategy to enhance diffusion through highly viscous SF. For that, two distinct NM actuating in “troops” were developed, capable of reducing SF viscosity and self-propel more effectively. The synergistic interaction between these NM systems significantly improved the transport of macromolecules across SF-mimicking environments, offering a potential strategy for intra-articular drug delivery in joint diseases. Building on these findings, the second part of this thesis continues within the same biomedical application framework but introduces key advancements in NM design. In this part, a new generation of nanogel-based NMs (NGs-NMs) composed of synthetic polymers are introduced to substitute the inorganic core of NMs. These NGs are soft and flexible, and enable motion in viscoelastic fluids while preserving the bulk rheological properties of SF. Their structural flexibility and tunable responsiveness to environmental changes (e.g., temperature, pH, or redox conditions) are achieved through controlled polymer crosslinking, enabling dynamic modulation of size and density allowing for improved interaction with ECMs. After surface functionalization with urease, NGs-NMs achieved efficient propulsion in viscous media at low urea concentrations. Importantly, they exhibited rapid cellular uptake and were further evaluated as active transport carriers for growth factors, as IGF-1, preserving the bioactivity of the conjugated IGF-1 and demonstrated pro-regenerative effects in chondrogenic cell model. The third part of this thesis further explores the application of NG-NMs for antimicrobial therapy, extending their use to other biomedical applications that require navigation across mucosal barriers for effective drug delivery. In this case, hyaluronic acid (HA), a naturally occurring mucoadhesive biopolymer, was employed as the core material to construct enzyme-powered nanomotors (HA-NMs) functionalized with urease. These HA-NMs were designed to actively cross mucin environments and deliver therapeutic agents, such as antibiotics. Their performance was assessed in mucosal models, highlighting their potential to overcome barriers associated, for instance, with antimicrobial resistance and enable targeted treatment at mucosal interfaces. Their performance was evaluated in vitro using mucosal models, including transwell assays, which confirmed their ability to penetrate mucin barriers and significantly reduced bacterial proliferation. When loaded with antibiotics, HA-NMs exhibited enhanced antibacterial activity against Escherichia coli compared to both free antibiotic and reference MSNPs-NMs from the first part of the thesis. The results presented in this thesis highlight the transformative potential of enzyme-powered NMs as highly versatile platforms for targeted therapeutic delivery. Their ability to actively navigate complex and viscous biological environments and enhance therapeutic efficacy represents an important breakthrough in the field of nanomedicine. These findings open the door for a new generation of self-propelled nanotherapeutics, bringing us closer to their clinical translation and opening new avenues for precision treatment in challenging pathological contexts. |
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