Silver nanoparticles (AgNPs) are the most investigated antibacterial agents against multidrug resistant (MDR) pathogens. They can lead to cellular death by means of different mechanisms, damaging several cell compartments, from the external membrane, to enzymes, DNA and proteins; this simultaneous attack amplifies the toxic effect on bacteria with respect to traditional antibiotics. The effectiveness of AgNPs against MDR bacteria is strongly correlated with their chemical and morphological properties, which influence the pathways involved in cellular damage. In this review, AgNPs’ size, shape and modification by functional groups or other materials are reported, both to investigate the different synthetic pathways correlated with nanoparticles’ modifications and to evaluate the related effect on their antibacterial activity. Indeed, understanding the synthetic conditions for obtaining performing antibacterial AgNPs could help to tailor new and improved silver-based agents to combat multidrug resistance.

Skin represents an effective barrier against the penetration of external agents into the human body. Nevertheless, recent research has shown that small particles, especially in the nanosized range, can not only penetrate through the skin but also work as vectors to transport active molecules such as contrast agents or drugs. This knowledge has opened new perspectives on nanomedicine and controlled drug delivery. On the other hand, micro- and nanoplastics represent a form of emerging pollutants, and their concentration in the environment has been reported to drastically increase in the last years. The possible penetration of these particles through the skin has become a major concern for human health. If the actual primary toxicity of these materials is still debated, their possible role in the transport of toxic molecules through the skin, originating as secondary toxicity, is surely alarming. In this review paper, we analyze and critically discuss the most recent scientific publications to underline how these two processes, (i) the controlled delivery of bioactive molecules by micro- and nano-structures and (ii) the unwanted and uncontrolled penetration of toxic species through the skin mediated by micro- and nanoparticles, are deeply related and their efficiency is strongly affected by the nature, size, and shape of the particles.

Nanosized antioxidants are highly advantageous in terms of versatility and pharmacokinetics, with respect to conventional molecular ones. Melanin-like materials, artificial species inspired by natural melanin, combine recognized antioxidant (AOX) activity with a unique versatility of preparation and modification. Due to this versatility and documented biocompatibility, artificial melanin has been incorporated into a variety of nanoparticles (NP) in order to give new platforms for nanomedicine with enhanced AOX activity. In this review article, we first discuss the chemical mechanisms behind the AOX activity of materials in the context of the inhibition of the radical chain reaction responsible for the peroxidation of biomolecules. We also focus briefly on the AOX properties of melanin-like NP, considering the effect of parameters such as size, preparation methods and surface functionalization on them. Then, we consider the most recent and relevant applications of AOX melanin-like NPs that are able to counteract ferroptosis and be involved in the treatment of important diseases that affect, e.g., the cardiovascular and nervous systems, as well as the kidneys, liver and articulations. A specific section will be dedicated to cancer treatment, since the role of melanin in this context is still very debated. Finally, we propose future strategies in AOX development for a better chemical understanding of melanin-like materials. In particular, the composition and structure of these materials are still debated, and they present a high level of variability. Thus, a better understanding of the mechanism behind the interaction of melanin-like nanostructures with different radicals and highly reactive species would be highly advantageous for the design of more effective and specific AOX nano-agents.

Recently, drug delivery strategies based on nanomaterials have attracted a lot of interest in different kinds of therapies because of their superior properties. Polydopamine (PDA), one of the most interesting materials in nanomedicine because of its versatility and biocompatibility, has been widely investigated in the drug delivery field. It can be easily functionalized to favor processes like cellular uptake and blood circulation, and it can also induce drug release through two kinds of stimuli: NIR light irradiation and pH. In this review, we describe PDA nanomaterials’ performance on drug delivery, based on their size, morphology, and surface charge. Indeed, these characteristics strongly influence the main mechanisms involved in a drug delivery system: blood circulation, cellular uptake, drug loading, and drug release. The understanding of the connections between PDA nanosystems’ properties and these phenomena is pivotal to obtain a controlled design of new nanocarriers based on the specific drug delivery applications.

Polydopamine (PDA), the synthetic counterpart of melanin, is a widely investigated bio-inspired material for its chemical and photophysical properties, and in the last few years, bio-application of PDA and PDA-based materials have had a dramatic increase. In this review, we described PDA application in optical biosensing, exploring its multiple roles as a nanomaterial. In optical sensing, PDA can not only be used for its intrinsic fluorescent and photoacoustic properties as a probe: in some cases, a sample optical signal can be derived by melanin generation in situ or it can be enhanced in another material thanks to PDA modification. The various possibilities of PDA use coupled with its biocompatibility will indeed widen even more its application in optical bioimaging.

Fluorescence, and more in general, photoluminescence (PL), presents important advantages for imaging with respect to other diagnostic techniques. In particular, detection methodologies exploiting fluorescence imaging are fast and versatile; make use of low-cost and simple instrumentations; and are taking advantage of newly developed powerful, low-cost, light-based electronic devices, such as light sources and cameras, used in huge market applications, such as civil illumination, computers, and cellular phones. Besides the aforementioned simplicity, fluorescence imaging offers a spatial and temporal resolution that can hardly be achieved with alternative methods. However, the two main limitations of fluorescence imaging for bio-application are still (i) the biological tissue transparency and autofluorescence and (ii) the biocompatibility of the contrast agents. Luminescent gold nanoclusters (AuNCs), if properly designed, combine high biocompatibility with PL in the near-infrared region (NIR), where the biological tissues exhibit higher transparency and negligible autofluorescence. However, the stabilization of these AuNCs requires the use of specific ligands that also affect their PL properties. The nature of the ligand plays a fundamental role in the development and sequential application of PL AuNCs as probes for bioimaging. Considering the importance of this, in this review, the most relevant and recent papers on AuNCs-based bioimaging are presented and discussed highlighting the different functionalities achieved by increasing the complexity of the ligand structure.