Skin penetration of active molecules for treatment of diverse diseases is a major field of research owing to the advantages associated with the skin like easy accessibility, reduced systemic‐derived side effects, and increased therapeutic efficacy. Despite these advantages, dermal drug delivery is generally challenging due to the low skin permeability of therapeutics. Although various methods have been developed to improve skin penetration and permeation of therapeutics, they are usually aggressive and could lead to irreversible damage to the stratum corneum. Nanosized carrier systems represent an alternative approach for current technologies, with minimal damage to the natural barrier function of skin. In this Review, the use of nanoparticles to deliver drug molecules, genetic material, and vaccines into the skin is discussed. In addition, nanotoxicology studies and the recent clinical development of nanoparticles are highlighted to shed light on their potential to undergo market translation.

Over the past two decades, nanotechnology has made significant progress toward the development and applications of micromotors (MMs) and nanomotors (NMs). Characterized by their capability to self-propel and swim in fluids, they have emerged as promising tools in various fields, particularly in biomedicine. This Review presents an overview of the current state of MMs and NMs, their motion in viscous media and complex environments, their interaction with biological barriers, and potential therapeutical applications. We identify the choice of appropriate administration routes to reach their target location as a key aspect of the success of MMs and NMs in biomedical applications. Looking ahead, we envision NMs playing a key role in treating diverse medical disorders, as recent proof-of-concept in vivo studies demonstrate their distinct capabilities and versatility. However, addressing regulatory, scalability, biocompatibility, and safety concerns remains imperative for the successful translation of NMs into clinical trials and industrial-scale production. This work provides a guideline for researchers, guiding them through the current landscape, challenges, and prospects of using MMs and NMs in biomedicine, thereby encouraging their responsible development and positioning in the future of nanomedicine. Furthermore, we outline critical areas for further research, including studies on biocompatibility, safety, and methods to overcome physical obstacles.

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.

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 field of nanophotonics has seen remarkable advances, with gold‐based materials standing out. By precisely fine‐tuning the size and shape of metal nanoparticles (NPs), such as gold nanoparticles (AuNPs), it has been possible to gain control over light interaction, modulating localized surface plasmon resonance (LSPR), a phenomenon that involves the collective oscillation of free conduction electrons. This has opened the path toward more powerful biomedical applications, including surface‐enhanced Raman spectroscopy (SERS) and photothermal therapy (PTT). When AuNPs dimensions fall below 2 nm, they become gold nanoclusters (AuNCs), losing the LSPR but acquitting fluorescence due to their molecule‐like behavior. This unique feature makes them ideal for high‐resolution imaging, biomarker detection, and advanced therapies. Beyond traditional uses, the recent inclusion of AuNPs into nanomotors (NMs) enhances precise in vivo tracking and targeted drug delivery. This review highlights the different applications of plasmonic nanomaterials with particular emphasis on AuNPs and AuNCs as a function of their shapes, sizes, and stabilization ligands. Moreover, it dives into the biosensing applications of plasmonic materials by addressing their so‐called far‐field and near‐field optical properties, giving a detailed overview of different high‐sensitivity immunoassays and biosensing. A comprehensive outlook on the evolution of plasmonic‐based materials for the next therapies is provided.

Anisotropic gold nanoparticles (AuNPs) are renowned for their unique properties – including localized surface plasmon resonance (LSPR) and adjustable optical responses to light exposure – that enable the conversion of light into heat and make them a promising tool in cancer therapy. Nonetheless, their tendency to aggregate and consequently lose their photothermal conversion capacity during prolonged irradiation periods represents a central challenge in developing anisotropic AuNPs for clinical use. To overcome this issue, an innovative approach that facilitates the encapsulation of individual anisotropic AuNPs within thin nanogels, forming hybrid nanomaterials that mirror the inorganic core's morphology while introducing a negligible (2–8 nm) increase in overall diameter is proposed. The encapsulation of rod‐ and star‐shaped anisotropic AuNPs within poly‐acrylamide (pAA) or poly‐(N‐isopropylacrylamide) (pNIPAM) nanogels is successfully demonstrated. The ultrathin polymeric layers display remarkable durability, significantly enhancing the photothermal stability of anisotropic AuNPs during their interaction with near‐infrared light and effectively boosting their photothermal capacities for extended irradiation periods. The outcomes of the research thus support the development of more stable and reliable AuNPs as hybrid nanomaterials, positioning them as promising nanomedicinal platforms.