The novel controlled and localized delivery of drug molecules to target tissues using an external electric stimulus makes electro-responsive drug delivery systems both feasible and desirable, as well as entailing a reduction in the side effects. Novel micro-scaffold matrices were designed based on poly(lactic acid) (PLA) and graphene oxide (GO) via electrospinning. Quercetin (Q), a natural flavonoid, was loaded into the fiber matrices in order to investigate the potential as a model drug for wound dressing applications. The physico-chemical properties, electrical triggering capacity, antimicrobial assay and biocompatibility were also investigated. The newly fabricated PLA/GO/Q scaffolds showed uniform and smooth surface morphologies, without any beads, and with diameters ranging from 1107 nm (10%PLA/0.1GO/Q) to 1243 nm (10%PLA). The in vitro release tests of Q from the scaffolds showed that Q can be released much faster (up to 8640 times) when an appropriate electric field is applied compared to traditional drug-release approaches. For instance, 10 s of electric stimulation is enough to ensure the full delivery of the loaded Q from the 10%PLA/1%GO/Q microfiber scaffold at both 10 Hz and at 50 Hz. The antimicrobial tests showed the inhibition of bacterial film growth. Certainly, these materials could be loaded with more potent agents for anti-cancer, anti-infection, and anti-osteoporotic therapies. The L929 fibroblast cells cultured on these scaffolds were distributed homogeneously on the scaffolds, and the highest viability value of 82.3% was obtained for the 10%PLA/0.5%GO/Q microfiber scaffold. Moreover, the addition of Q in the PLA/GO matrix stimulated the production of IL-6 at 24 h, which could be linked to an acute inflammatory response in the exposed fibroblast cells, as a potential effect of wound healing. As a general conclusion, these results demonstrate the possibility of developing graphene oxide-based supports for the electrically triggered delivery of biological active agents, with the delivery rate being externally controlled in order to ensure personalized release.

The purpose of this study was to construct and characterize iron oxide nanoparticles (IONP_CO) for intracellular delivery of the anthracycline doxorubicin (DOX; IONP_DOX) in order to induce tumor cell inactivation. More than 80% of the loaded drug was released from IONP_DOX within 24 h (100% at 70 h). Efficient internalization of IONP_DOX and IONP_CO in HeLa cells occurred through pino- and endocytosis, with both IONP accumulating in a perinuclear pattern. IONP_CO were biocompatible with maximum 27.9% ± 6.1% reduction in proliferation 96 h after treatment with up to 200 µg/mL IONP_CO. Treatment with IONP_DOX resulted in a concentration- and time-dependent decrease in cell proliferation (IC₅₀ = 27.5 ± 12.0 μg/mL after 96 h) and a reduced clonogenic survival (surviving fraction, SF = 0.56 ± 0.14; versus IONP_CO (SF = 1.07 ± 0.38)). Both IONP constructs were efficiently internalized and retained in the cells, and IONP_DOX efficiently delivered DOX resulting in increased cell death vs IONP_CO.

Chondrosarcoma is a malignant cartilaginous tumor that is particularly chemoresistant and radioresistant to X-rays. The first line of treatment is surgery, though this is almost impossible in some specific locations. Such resistances can be explained by the particular composition of the tumor, which develops within a dense cartilaginous matrix, producing a resistant area where the oxygen tension is very low. This microenvironment forces the cells to adapt and dedifferentiate into cancer stem cells, which are described to be more resistant to conventional treatments. One of the main avenues considered to treat this type of tumor is hadrontherapy, in particular for its ballistic properties but also its greater biological effectiveness against tumor cells. In this review, we describe the different forms of chondrosarcoma resistance and how hadrontherapy, combined with other treatments involving targeted inhibitors, could help to better treat high-grade chondrosarcoma.

Nanotechnology has been successfully used for the fabrication of targeted anti-cancer drug carriers. This study aimed to obtain Fe₃O₄ nanoparticles functionalized with Gemcitabine to improve the cytotoxic effects of the chemotherapeutic substance on cancer cells. The (un) functionalized magnetite nanoparticles were synthesized using a modified co-precipitation method. The nanoconjugate characterization was performed by XRD, SEM, SAED and HRTEM; the functionalizing of magnetite with anti-tumor substances has been highlighted through TGA. The interaction with biologic media has been studied by means of stability and agglomeration tendency (using DLS and Zeta Potential); also, the release kinetics of the drug in culture media was evaluated. Cytotoxicity of free-Gemcitabine and the obtained nanoconjugate were evaluated on human BT 474 breast ductal carcinoma, HepG2 hepatocellular carcinoma and MG 63 osteosarcoma cells by MTS. In parallel, cellular morphology of these cells were examined through fluorescence microscopy and SEM. The localization of the nanoparticles related to the cells was studied using SEM, EDX and TEM. Hemolysis assay showed no damage of erythrocytes. Additionally, an in vivo biodistribution study was made for tracking where Fe₃O₄@Gemcitabine traveled in the body of mice. Our results showed that the transport of the drug improves the cytotoxic effects in comparison with the one produced by free Gemcitabine for the BT474 and HepG2 cells. The in vivo biodistribution test proved nanoparticle accumulation in the vital organs, with the exception of spleen, where black-brown deposits have been found. These results indicate that our Gemcitabine-functionalized nanoparticles are a promising targeted system for applications in cancer therapy.