Oxidative stress represents a common issue in most neurological diseases, causing severe impairments of neuronal cell physiological activity that ultimately lead to neuron loss of function and cellular death. In this work, lipid-coated polydopamine nanoparticles (L-PDNPs) are proposed both as antioxidant and neuroprotective agents, and as a photothermal conversion platform able to stimulate neuronal activity. L-PDNPs showed the ability to counteract reactive oxygen species (ROS) accumulation in differentiated SH-SY5Y, prevented mitochondrial ROS-induced dysfunctions and stimulated neurite outgrowth. Moreover, for the first time in the literature, the photothermal conversion capacity of L-PDNPs was used to increase the intracellular temperature of neuron-like cells through near-infrared (NIR) laser stimulation, and this phenomenon was thoroughly investigated using a fluorescent temperature-sensitive dye and modeled from a mathematical point of view. It was also demonstrated that the increment in temperature caused by the NIR stimulation of L-PDNPs was able to produce a Ca 2+ influx in differentiated SH-SY5Y, being, to the best of our knowledge, the first example of organic nanostructures used in such an approach. This work could pave the way to new and exciting applications of polydopamine-based and of other NIR-responsive antioxidant nanomaterials in neuronal research.

Polydopamine (PDA) is a polymer that derives from the self-polymerization of the biomolecule dopamine. It can be easily synthesized to obtain spherical nanoparticles (PDNPs), tunable in terms of size, loaded cargo, and surface functionalization. PDNPs have been increasingly attracting the attention of the research community due to their elevated versatility in the biomedicine field, for their excellent ability to encapsulate drugs, to convert near-infrared (NIR) radiation into heat, and to act as an antioxidant agent. Size is an important aspect to be considered, especially concerning the specific intended field of application. This work aims at investigating how changes in the size of PDNPs affect the nanoparticle properties relevant for biomedical applications, especially focusing on cancer nanomedicine. A library of differently sized PDNPs (from 145 to 957 nm) has been obtained by varying the ammonia/dopamine molar ratio during the synthesis procedure, and detailed characterization in terms of biocompatibility, cell internalization, antioxidant capacity, and photothermal conversion has been carried out. Experiments showed that nanoparticles with a larger diameter display higher NIR absorbance, superior resistance to degradation, and higher photothermal conversion capacity (the latter confirmed by a mathematical model). On the other hand, a reduction in diameter size induces both improved antioxidant properties and enhanced cellular uptake. Herein, we provide a useful tool, allowing one to choose the proper size of PDNPs tailored for specific biomedical applications.

Reactive oxygen species (ROS) are active molecules involved in several biological functions. When the production of ROS is not counterbalanced by the action of protective antioxidant mechanisms present in living...

In recent years, the need for highly predictive brain cancer models to test new anticancer compounds and experimental therapeutic approaches has significantly increased. Realistic in vitro brain tumor-on-a-chip platforms would allow a more accurate selection of valid candidate drugs and nanomedicines, therefore alleviating the economic and ethical issues of unsuccessful studies in vivo. Here, we present a multi-functional self-assembled brain tumor-on-a-chip model characterized by 3D glioma cultures interfaced both to nonmalignant brain cells of the peritumoral niche and to a 3D-real-scale blood–brain barrier (BBB) microfluidic system. This platform allowed us to screen multiple features, such as BBB crossing capabilities, apoptotic efficacy against GBM cells, and side effects on nonmalignant brain cells of a promising anticancer drug, nutlin-3a, which is fundamental for the treatment of brain cancer.

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Prostate malignancy represents the second leading cause of cancer-specific death among the male population worldwide. Herein, enhanced intracellular magnetic fluid hyperthermia is applied in vitro to treat prostate cancer (PCa) cells with minimum invasiveness and toxicity and highly specific targeting. We designed and optimized novel shape-anisotropic magnetic core–shell–shell nanoparticles (i.e., trimagnetic nanoparticles - TMNPs) with significant magnetothermal conversion following an exchange coupling effect to an external alternating magnetic field (AMF). The functional properties of the best candidate in terms of heating efficiency (i.e., Fe3O4@Mn0.5Zn0.5Fe2O4@CoFe2O4) were exploited following surface decoration with PCa cell membranes (CM) and/or LN1 cell-penetrating peptide (CPP). We demonstrated that the combination of biomimetic dual CM-CPP targeting and AMF responsiveness significantly induces caspase 9-mediated apoptosis of PCa cells. Furthermore, a downregulation of the cell cycle progression markers and a decrease of the migration rate in surviving cells were observed in response to the TMNP-assisted magnetic hyperthermia, suggesting a reduction in cancer cell aggressiveness.