Enhancing Proton Radiosensitivity of Chondrosarcoma Using Nanoparticle-Based Drug Delivery Approaches: A Comparative Study of High- and Low-Energy Protons.

To overcome chondrosarcoma's (CHS) high chemo- and radioresistance, we used polyethylene glycol-encapsulated iron oxide nanoparticles (IONPs) for the controlled delivery of the chemotherapeutic doxorubicin (IONP) to amplify the cytotoxicity of proton radiation therapy. Human 2D CHS SW1353 cells were treated with protons (linear energy transfer (LET): 1.6 and 12.

Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET.

Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction with surgery, but with a generally low efficiency.

Unveiling Nanoparticles: Recent Approaches in Studying the Internalization Pattern of Iron Oxide Nanoparticles in Mono- and Multicellular Biological Structures.

Nanoparticle (NP)-based solutions for oncotherapy promise an improved efficiency of the anticancer response, as well as higher comfort for the patient. The current advancements in cancer treatment based on nanotechnology exploit the ability of these systems to pass biological barriers to target the tumor cell, as well as tumor cell organelles. In particular, iron oxide NPs are being clinically employed in oncological management due to this ability.

In vitro hyperspectral biomarkers of human chondrosarcoma cells in nanoparticle-mediated radiosensitization using carbon ions.

New therapeutic approaches are needed for the management of the highly chemo- and radioresistant chondrosarcoma (CHS). In this work, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the intracellular delivery of the chemotherapeutic doxorubicin (IONP) to augment the cytotoxic effects of carbon ions in comparison to photon radiation therapy. The in vitro biological effects were investigated in SW1353 chondrosarcoma cells focusing on the following parameters: cell survival using clonogenic test, detection of micronuclei (MN) by cytokinesis blocked micronucleus assay and morphology together with spectral fingerprints of nuclei using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module.

Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions.

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.

Impaired Integrated Stress Response and Mitochondrial Integrity Modulate Genotoxic Stress Impact and Lower the Threshold for Immune Signalling.

Mitochondria-nucleus communication during stress dictates cellular fate with consequences on the etiopathology of multiple age-related diseases. Impaired mitochondrial quality control through loss of function of the mitochondrial protease HtrA2 associates with accumulation of damaged mitochondria and triggers the integrated stress response, implicating the transcription factor CHOP. Here we have employed a combined model of impaired mitochondria quality control, namely HtrA2 loss of function, and/or integrated stress response, namely CHOP loss of function, and genotoxicity to address the distinctive roles of these cellular components in modulating intracellular and intercellular responses.

Nanoparticle-Mediated Drug Delivery of Doxorubicin Induces a Differentiated Clonogenic Inactivation in 3D Tumor Spheroids In Vitro.

Involvement of 3D tumor cell models in the in vitro biological testing of novel nanotechnology-based strategies for cancer management can provide in-depth information on the real behavior of tumor cells in complex biomimetic architectures. Here, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the controlled delivery of a doxorubicin chemotherapeutic substance (IONP), and to enhance cytotoxicity of photon radiation therapy. The biological effects of nanoparticles and 150 kV X-rays were evaluated on both 2D and 3D cell models of normal human keratinocytes (HaCaT) and tumor cells-human cervical adenocarcinoma (HeLa) and human squamous carcinoma (FaDu)-through cell survival.

Novel Antitumor Agents Based on Fluorescent Benzofurazan Derivatives and Mesoporous Silica.

Two novel fluorescent mesoporous silica-based hybrid materials were obtained through the covalent grafting of [4-hydrazinyl-7-nitrobenz-[2,1,3-]-oxadiazole (NBDH) and N-(7-nitrobenzo[][1,2,5]-oxadiazol-4-yl) benzene-1,2-diamine (NBD-PD), respectively, inside the channels of mesoporous silica SBA-15. The presence of fluorescent organic compounds (nitrobenzofurazan derivatives) was confirmed by infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), thermal analysis (TG), and fluorescence spectroscopy. The nitrogen physisorption analysis showed that the nitrobenzofurazan derivatives were distributed uniformly on the internal surface of SBA-15, the immobilization process having a negligible effect on the structure of the support.

Mitochondria - Nucleus communication in neurodegenerative disease. Who talks first, who talks louder?

Mitochondria - nuclear coadaptation has been central to eukaryotic evolution. The dynamic dialogue between the two compartments within the context of multiorganellar interactions is critical for maintaining cellular homeostasis and directing the balance survival-death in case of cellular stress. The conceptualisation of mitochondria - nucleus communication has so far been focused on the communication from the mitochondria under stress to the nucleus and the consequent signalling responses, as well as from the nucleus to mitochondria in the context of DNA damage and repair.

Development of New Collagen/Clay Composite Biomaterials.

The fabrication of collagen-based biomaterials for skin regeneration offers various challenges for tissue engineers. The purpose of this study was to obtain a novel series of composite biomaterials based on collagen and several types of clays. In order to investigate the influence of clay type on drug release behavior, the obtained collagen-based composite materials were further loaded with gentamicin.

Intracellular Delivery of Doxorubicin by Iron Oxide-Based Nano-Constructs Increases Clonogenic Inactivation of Ionizing Radiation in HeLa Cells.

In this study, we determined the potential of polyethylene glycol-encapsulated iron oxide nanoparticles (IONP) for the intracellular delivery of the chemotherapeutic doxorubicin (IONP) to enhance the cytotoxic effects of ionizing radiation. The biological effects of IONP and X-ray irradiation (50 kV and 6 MV) were determined in HeLa cells using the colony formation assay (CFA) and detection of γH2AX foci. Data are presented as mean ± SEM.

Benzofurazan derivatives modified graphene oxide nanocomposite: Physico-chemical characterization and interaction with bacterial and tumoral cells.

Two novel graphene oxide-benzofuran derivatives composites were obtained through the covalent immobilization of [4-hydrazinyl-7nitrobenz-[2,1,3-d]-oxadiazole (NBDH) and respectively, N1-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)benzene-1,2-diamine (NBD-PD), on graphene oxide. This covalent functionalization was achieved by activating the carboxylic groups on the surface of graphene oxide by the reaction with thionyl chloride followed by coupling with the amino group of benzofurazane derivatives to obtain the NBD derivatives grafted on graphene oxide. The formation of new materials was check by Raman spectroscopy, fluorescence, infrared spectroscopy and X-ray photoelectron spectroscopy, thermal analysis, scanning electron microscopy, and elemental mapping.

Enhanced Internalization of Nanoparticles Following Ionizing Radiation Leads to Mitotic Catastrophe in MG-63 Human Osteosarcoma Cells.

This study aims to investigate whether ionizing radiation combined with doxorubicin-conjugated iron oxide nanoparticles (NP-DOX) improves the internalization and cytotoxic effects of the nano-carrier-mediated drug delivery in MG-63 human osteosarcoma cells. NP-DOX was designed and synthesized using the co-precipitation method. Highly stable and crystalline nanoparticles conjugated with DOX were internalized in MG-63 cells through macropinocytosis and located in the perinuclear area.

Intracellular and Intercellular Signalling Mechanisms following DNA Damage Are Modulated By PINK1.

Impaired mitochondrial function and accumulation of DNA damage have been recognized as hallmarks of age-related diseases. Mitochondrial dysfunction initiates protective signalling mechanisms coordinated at nuclear level particularly by modulating transcription of stress signalling factors. In turn, cellular response to DNA lesions comprises a series of interconnected complex protective pathways, which require the energetic and metabolic support of the mitochondria.