Polydopamine Nanoparticles as an Organic and Biodegradable Multitasking Tool for Neuroprotection and Remote Neuronal Stimulation.

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 Ca2+ 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.

CeO2 Nanoparticles-Loaded pH-Responsive Microparticles with Antitumoral Properties as Therapeutic Modulators for Osteosarcoma.

Osteosarcoma is an aggressive form of bone cancer mostly affecting young people. To date, the most effective strategy for the treatment of osteosarcoma is the surgical removal of the tumor with or without combinational chemotherapy. In this study, we present the development of a pH-sensitive drug-delivery system in the form of microparticles, with increased chemotherapeutic action against the osteosarcoma cell line SAOS-2, and with reduced toxicity against the heart myoblastic cell line H9C2. The delivery system is composed of calcium carbonate and collagen type I, and is loaded with cerium dioxide (CeO2) nanoparticles (<25 nm) and the anticancer drug doxorubicin. The fabricated microparticles were fully characterized morphologically and physicochemically, and their ability to induce or inhibit apoptosis/necrosis was assessed using in vitro functional assays and flow cytometry. The results presented in this study show that the highest concentration (250 µg/mL) of the therapeutic microparticles (CaCO3-based therapeutic modulators (C-TherMods)), which corresponds to 6.4 µg/mL of encapsulated doxorubicin, can protect the H9C2 cells even after 120 h, since the percentage of viable cells at this time point is 65%. On the contrary, when H9C2 cells are treated with 0.5 µg/mL of free doxorubicin, 75% of the cells are dead only after 24 h. When SAOS-2 cells are treated with the same concentration of C-TherMods (250 µg/mL), the viability of SAOS-2 cells is 80% after 24 h, while it reduces to 50% after 120 h. At pH 6.0, the synergic effect of the pro-oxidant CeO2 nanoparticles and of the encapsulated doxorubicin leads to almost 100% of cell death, even at the lowest concentration of C-TherMods (50 µg/mL).