Monitoring Stress Response Difference in Nucleolus Morphology and ATP Content Changes during Hyperthermia Cell Apoptosis with Plasmonic Fluorescent Nanoprobes.

The nucleolus, as a main "cellular stress receptor", is the hub of the stress response driving cancer development and has great research value in the field of organelle-targeting photothermal therapy. However, there are few studies focused on monitoring nucleolar stress response and revealing how the energy metabolism of cells regulates the nucleolar stress response during photothermal therapy. Herein, by designing a nucleolus-targeting and ATP- and photothermal-responsive plasmonic fluorescent nanoprobe (AuNRs-CDs) based on gold nanorods (AuNRs) and fluorescent carbon quantum dots (CDs), we achieved real-time fluorescence imaging of nucleus morphology while monitoring changes of ATP content at the subcellular level. We found that the green fluorescence diminished at 5 min of photothermal therapy, and the nucleolus morphology began to shrink and became smaller in cancerous HepG2 cells. In contrast, there is no significant change of green fluorescence in the nucleolar region of normal HL-7702 cells. ATP content monitoring also showed similar results. Apparently, in response to photothermal stimuli, cancerous cells produce more ATP (energy) along with obvious change in nucleolus morphology and state compared to normal cells under the hyperthermia-induced cell apoptosis. The developed AuNRs-CDs as a nucleolus imaging nanoprobe and effective photothermal agent present promising applications for nucleolar stress studies and targeted photothermal therapy.

Nuclear Fragility in Radiation-Induced Senescence: Blebs and Tubes Visualized by 3D Electron Microscopy.

Irreparable DNA damage following ionizing radiation (IR) triggers prolonged DNA damage response and induces premature senescence. Cellular senescence is a permanent state of cell-cycle arrest characterized by chromatin restructuring, altered nuclear morphology and acquisition of secretory phenotype, which contributes to senescence-related inflammation. However, the mechanistic connections for radiation-induced DNA damage that trigger these senescence-associated hallmarks are poorly understood. In our in vitro model of radiation-induced senescence, mass spectrometry-based proteomics was combined with high-resolution imaging techniques to investigate the interrelations between altered chromatin compaction, nuclear envelope destabilization and nucleo-cytoplasmic chromatin blebbing. Our findings confirm the general pathophysiology of the senescence-response, with disruption of nuclear lamin organization leading to extensive chromatin restructuring and destabilization of the nuclear membrane with release of chromatin fragments into the cytosol, thereby activating cGAS-STING-dependent interferon signaling. By serial block-face scanning electron microscopy (SBF-SEM) whole-cell datasets were acquired to investigate the morphological organization of senescent fibroblasts. High-resolution 3-dimensional (3D) reconstruction of the complex nuclear shape allows us to precisely visualize the segregation of nuclear blebs from the main nucleus and their fusion with lysosomes. By multi-view 3D electron microscopy, we identified nanotubular channels formed in lamin-perturbed nuclei of senescent fibroblasts; the potential role of these nucleo-cytoplasmic nanotubes for expulsion of damaged chromatin has to be examined.

Atomic structure of Lanreotide nanotubes revealed by cryo-EM.

Functional and versatile nano- and microassemblies formed by biological molecules are found at all levels of life, from cell organelles to full organisms. Understanding the chemical and physicochemical determinants guiding the formation of these assemblies is crucial not only to understand the biological processes they carry out but also to mimic nature. Among the synthetic peptides forming well-defined nanostructures, the octapeptide Lanreotide has been considered one of the best characterized, in terms of both the atomic structure and its self-assembly process. In the present work, we determined the atomic structure of Lanreotide nanotubes at 2.5-Å resolution by cryoelectron microscopy (cryo-EM). Surprisingly, the asymmetric unit in the nanotube contains eight copies of the peptide, forming two tetramers. There are thus eight different environments for the peptide, and eight different conformations in the nanotube. The structure built from the cryo-EM map is strikingly different from the molecular model, largely based on X-ray fiber diffraction, proposed 20 y ago. Comparison of the nanotube with a crystal structure at 0.83-Å resolution of a Lanreotide derivative highlights the polymorphism for this peptide family. This work shows once again that higher-order assemblies formed by even well-characterized small peptides are very difficult to predict.

In vitro and in vivo MRI imaging and photothermal therapeutic properties of Hematite (α-Fe2O3) Nanorods.

Herein we report synthesis of hematite (α-Fe2O3) nanorods by calcinating hydrothermally synthesized goethite nanorods at 5000C. The structural, optical and MRI imaging guided cancer therapeutic properties of fabricated nanorods have been discussed in this manscript. FESEM and TEM imaging techniques were used to confirm the nanorod like morphology of as prepared materials. As we know that Fe2O3 nanorods with size in the range of 25-30 nm exhibit super magnetism. After coating with the PEG, the as prepared nanorods can be used as T2 MR imaging contrast agents. An excellent T2 MRI contrast of 38.763 mM-1s-1 achieved which is highest reported so far for α-Fe2O3. Besides the as prepared nanorods display an excellent photothermal conversion efficiency of 39.5% thus acts as an excellent photothermal therapeutic agent. Thus, we envision the idea of testing our nanorods for photothermal therapy and MR imaging application both in vitro and in vivo, achieving an excellent T2 MRI contrast and photothermal therapy effect with as prepared PEGylated nanorods.

Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells.

Cancer progresses by evading the immune system. Elucidating diverse immune evasion strategies is a critical step in the search for next-generation immunotherapies for cancer. Here we report that cancer cells can hijack the mitochondria from immune cells via physical nanotubes. Mitochondria are essential for metabolism and activation of immune cells. By using field-emission scanning electron microscopy, fluorophore-tagged mitochondrial transfer tracing and metabolic quantification, we demonstrate that the nanotube-mediated transfer of mitochondria from immune cells to cancer cells metabolically empowers the cancer cells and depletes the immune cells. Inhibiting the nanotube assembly machinery significantly reduced mitochondrial transfer and prevented the depletion of immune cells. Combining a farnesyltransferase and geranylgeranyltransferase 1 inhibitor, namely, L-778123, which partially inhibited nanotube formation and mitochondrial transfer, with a programmed cell death protein 1 immune checkpoint inhibitor improved the antitumour outcomes in an aggressive immunocompetent breast cancer model. Nanotube-mediated mitochondrial hijacking can emerge as a novel target for developing next-generation immunotherapy agents for cancer.

Tunneling nanotubes and related structures: molecular mechanisms of formation and function.

Tunneling nanotubes (TNTs) are F-actin-based, membrane-enclosed tubular connections between animal cells that transport a variety of cellular cargo. Over the last 15 years since their discovery, TNTs have come to be recognized as key players in normal cell communication and organism development, and are also exploited for the spread of various microbial pathogens and major diseases like cancer and neurodegenerative disorders. TNTs have also been proposed as modalities for disseminating therapeutic drugs between cells. Despite the rapidly expanding and wide-ranging relevance of these structures in both health and disease, there is a glaring dearth of molecular mechanistic knowledge regarding the formation and function of these important but enigmatic structures. A series of fundamental steps are essential for the formation of functional nanotubes. The spatiotemporally controlled and directed modulation of cortical actin dynamics would be required to ensure outward F-actin polymerization. Local plasma membrane deformation to impart negative curvature and membrane addition at a rate commensurate with F-actin polymerization would enable outward TNT elongation. Extrinsic tactic cues, along with cognate intrinsic signaling, would be required to guide and stabilize the elongating TNT towards its intended target, followed by membrane fusion to create a functional TNT. Selected cargoes must be transported between connected cells through the action of molecular motors, before the TNT is retracted or destroyed. This review summarizes the current understanding of the molecular mechanisms regulating these steps, also highlighting areas that deserve future attention.

Effect of bassorin (derived from gum tragacanth) and halloysite nanotubes on physicochemical properties and the osteoconductivity of methylcellulose-based injectable hydrogels.

Injectable hydrogels have been known as promising materials for the regeneration of irregular shape tissue defects. In this study, novel thermosensitive methylcellulose (MC) hydrogels containing bassorin (Ba) and halloysite nanotubes (HNTs) have been developed for application in bone tissue engineering. Bassorin isolated from gum tragacanth (GT) with the concentration of 0.25-1.5 w/v% was blended with MC. The best MC/Ba gel (containing 0.5% bassorin) was chosen based on the results of injectability and rheological tests. HNTs (1-7%) were added to this formulation and tested for the physicochemical, mechanical, rheological, degradation, swelling, and biological properties. In vitro biological evaluations including cell proliferation (by MTT assay), cell attachment (by SEM), osteogenic activity (by Alizarin Red staining and alkaline phosphatase assay), and osteogenic gene expression (by quantitative real-time polymerase chain reaction) were done using MG-63 cells. Results showed that bassorin led to the increased gel-forming ability (at a lower temperature) and mechanical properties of MC hydrogel. The presence of HNTs and bassorin affected the degradation rate and swelling degree of MC-based hydrogel. Results showed significant enhancement in cell proliferation, differentiation, and mineralization, as well as higher bone-specific gene expression of the cell on bassorin and HNTs incorporated MC compared to pure MC hydrogel.

Membrane nanotubes are ancient machinery for cell-to-cell communication and transport. Their interference with the immune system.

Nanotubular connections between mammalian cell types came into the focus only two decades ago, when "live cell super-resolution imaging" was introduced. Observations of these long-time overlooked structures led to understanding mechanisms of their growth/withdrawal and exploring some key genetic and signaling factors behind their formation. Unbelievable level of multiple supportive collaboration between tumor cells undergoing cytotoxic chemotherapy, cross-feeding" between independent bacterial strains or "cross-dressing" collaboration of immune cells promoting cellular immune response, all via nanotubes, have been explored recently. Key factors and "calling signals" determining the spatial directionality of their growth and their overall in vivo significance, however, still remained debated. Interestingly, prokaryotes, including even ancient archaebacteria, also seem to use such NT connections for intercellular communication. Herein, we will give a brief overview of current knowledge of membrane nanotubes and depict a simple model about their possible "historical role".

In vitro and in vivo detection of tunneling nanotubes in normal and pathological osteoclastogenesis involving osteoclast fusion.

Osteoclasts are multinucleated cells formed through specific recognition and fusion of mononuclear osteoclast precursors derived from hematopoietic stem cells. Detailed cellular events concerning cell fusion in osteoclast differentiation remain ambiguous. Tunneling nanotubes (TNTs), actin-based membrane structures, play an important role in intercellular communication between cells. We have previously reported the presence of TNTs in the fusion process of osteoclastogenesis. Here we analyzed morphological details of TNTs using scanning electron microscopy. The osteoclast precursor cell line RAW-D was stimulated to form osteoclast-like cells, and morphological details in the appearance of TNTs were extensively analyzed. Osteoclast-like cells could be classified into three types; early osteoclast precursors, late osteoclast precursors, and multinucleated osteoclast-like cells based on the morphological characteristics. TNTs were frequently observed among these three types of cells. TNTs could be classified into thin, medium, and thick TNTs based on the diameter and length. The shapes of TNTs were dynamically changed from thin to thick. Among them, medium TNTs were often observed between two remote cells, in which side branches attached to the culture substrates and beaded bulge-like structures were often observed. Cell-cell interaction through TNTs contributed to cell migration and rapid transport of information between cells. TNTs were shown to be involved in cell-cell fusion between osteoclast precursors and multinucleated osteoclast-like cells, in which movement of membrane vesicles and nuclei was observed. Formation of TNTs was also confirmed in primary cultures of osteoclasts. Furthermore, we have successfully detected TNTs formed between osteoclasts observed in the bone destruction sites of arthritic rats. Thus, formation of TNTs may be important for the differentiation of osteoclasts both in vitro and in vivo. TNTs could be one target cellular structure for the regulation of osteoclast differentiation and function in bone diseases.

Multifunctional palygorskite@ZnO nanorods enhance simultaneously mechanical strength and antibacterial properties of chitosan-based film.

A general and effective strategy was developed for improving simultaneously the mechanical strength and antibacterial performance of biopolymer-based films. The well-dispersed zinc oxide (ZnO) nanoparticles were in-situ loaded on non-toxic natural palygorskite (PAL) nanorod to form an antibacterial PAL@ZnO composite nanorod, which can be embedded into chitosan/gelatin (CS/GL) film to produce the composite films with noticeably enhanced mechanical properties and antibacterial activity against S. aureus and E. coli bacteria (inhibition zones are 21.82 ± 0.95 mm and 16.36 ± 1.64 mm, respectively). The toughness of films enhances to 35.13 ± 0.95 MPa and the moisture uptake decreases to 23.74 ± 0.02% after embedding 3% and 9% of PAL@ZnO, respectively. In addition, incorporating PAL@ZnO nanorods also significantly enhanced the water resistance, and thermal stability of film. This work provides an alternative way for the development of antibacterial films with potential applications in many fields such as food packing.

A synthetic tubular molecular transport system.

Creating artificial macromolecular transport systems that can support the movement of molecules along defined routes is a key goal of nanotechnology. Here, we report the bottom-up construction of a macromolecular transport system in which molecular pistons diffusively move through micrometer-long, hollow filaments. The pistons can cover micrometer distances in fractions of seconds. We build the system using multi-layer DNA origami and analyze the structures of the components using transmission electron microscopy. We study the motion of the pistons along the tubes using single-molecule fluorescence microscopy and perform Langevin simulations to reveal details of the free energy surface that directs the motions of the pistons. The tubular transport system achieves diffusivities and displacement ranges known from natural molecular motors and realizes mobility improvements over five orders of magnitude compared to previous artificial random walker designs. Electric fields can also be employed to actively pull the pistons along the filaments, thereby realizing a nanoscale electric rail system. Our system presents a platform for artificial motors that move autonomously driven by chemical fuels and for performing nanotribology studies, and it could form a basis for future molecular transportation networks.

Reusable, Noninvasive, and Sensitive Fluorescence Enhanced ZnO-Nanorod-Based Microarrays for Quantitative Detection of AFP in Human Serum.

The fabrication of sensitive protein microarrays such as PCR used in DNA microarray is challenging due to lack of signal amplification. The development of microarrays is utilized to improve the sensitivity and limitations of detection towards primal cancer detection. The sensitivity is enhanced by the use of ZnO-nanorods and is investigated as a substrate which enhance the florescent signal to diagnose the hepatocellular carcinoma (HCC) at early stages. The substrate for deposition of ZnO-nanorods is prepared by the conventional chemical bath deposition method. The resultant highly dense ZnO-nanorods enhance the fluorescent signal 7.2 times as compared to the substrate without ZnO-nanorods. The microarray showed sensitivity of 1504.7 ng ml-1 and limit of detection of 0.1 pg ml-1 in wide dynamic range of 0.05 pg-10 µg ml-1 for alpha fetoprotein (AFP) detection in 10% human serum. This immunoassay was successfully applied for human serum samples to detect tumor marker with good recoveries. The ZnO-nanorod substrate is a simple protein microarray which showed a great promise for developing a low-cost, sensitive, and high-throughput protein assay platform for several applications in both fundamental research and clinical diagnosis.

Fabrication of 2D-MoSe2 incorporated NiO Nanorods modified electrode for selective detection of glucose in serum samples.

Layered molybdenum diselenide (MoSe2) nanosheets were formed by the weak Van der Waals forces of attraction between Se and Mo atoms. MoSe2 has a larger space between the adjacent layers and smaller band gaps in the range of 0.85 to ~ 1.6 eV. In this study, MoSe2 nanosheets decorated nickel oxide (NiO) nanorods have been synthesized by hydrothermal method using sodium molybdate and selenium metal powder. NiO/MoSe2 composite formation was confirmed by powder X-ray diffraction analysis. In addition, the presence of MoSe2 nanosheets on NiO nanorods were confirmed by field emission scanning electron microscopy, high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy. The Nyquist plots of NiO/MoSe2 coated glassy carbon electrode (GCE) was indicated that it had lower charge transfer resistance compared to NiO/GCE and MoSe2/GCE. Furthermore, as-prepared NiO/MoSe2/GCE was used to detect glucose in alkaline solution by cyclic voltammetry and amperometry techniques. The NiO/MoSe2/GCE was exhibited a linear response for the oxidation of glucose from 50 µM to 15.5 mM (R2 = 0.9842) at 0.5 V by amperometry. The sensor response time and the limit of detection were found to be 2 s and 0.6 µM for glucose. Moreover, selectivity of the NiO/MoSe2 sensor was tested in the presence of common interferent molecules such as hydrogen peroxide, fructose, lactose, ascorbic acid, uric acid, and dopamine. It was found that NiO/MoSe2/GCE did not respond to these interfering biomolecules. In addition, NiO/MoSe2/GCE had shown high stability, reproducibility and repeatability. Finally, the practical application of the sensor was demonstrated by detecting glucose in human blood serum with the acceptable recovery.

Fast photothermal spatial light modulation for quantitative phase imaging at the nanoscale.

Spatial light modulators have become an essential tool for advanced microscopy, enabling breakthroughs in 3D, phase, and super-resolution imaging. However, continuous spatial-light modulation that is capable of capturing sub-millisecond microscopic motion without diffraction artifacts and polarization dependence is challenging. Here we present a photothermal spatial light modulator (PT-SLM) enabling fast phase imaging for nanoscopic 3D reconstruction. The PT-SLM can generate a step-like wavefront change, free of diffraction artifacts, with a high transmittance and a modulation efficiency independent of light polarization. We achieve a phase-shift > π and a response time as short as 70 µs with a theoretical limit in the sub microsecond range. We used the PT-SLM to perform quantitative phase imaging of sub-diffractional species to decipher the 3D nanoscopic displacement of microtubules and study the trajectory of a diffusive microtubule-associated protein, providing insights into the mechanism of protein navigation through a complex microtubule network.

Citrate-Stabilized Gold Nanorods-Directed Osteogenic Differentiation of Multiple Cells.

OBJECTIVE: Gold nanorods (AuNRs) show great potential for versatile biomedical applications, such as stem cell therapy and bone tissue engineering. However, as an indispensable shape-directing agent for the growth of AuNRs, cetyltrimethylammonium bromide (CTAB) is not optimal for biological studies because it forms a cytotoxic bilayer on the AuNR surface, which interferes with the interactions with biological cells. METHODS: Citrate-stabilized AuNRs with various aspect-ratios (Cit-NRI, Cit-NRII, and Cit-NRIII) were prepared by the combination of end-selective etching and poly(sodium 4-styrenesulfonate)-assisted ligand exchange method. Their effects on osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1), rat bone marrow mesenchymal stem cells (rBMSCs), and human periodontal ligament progenitor cells (PDLPs) have been investigated. Potential signaling pathway of citrate-stabilized AuNRs-induced osteogenic effects was also investigated. RESULTS: The experimental results showed that citrate-stabilized AuNRs have superior biocompatibility and undergo aspect-ratio-dependent osteogenic differentiation via expression of osteogenic marker genes, alkaline phosphatase (ALP) activity and formation of mineralized nodule. Furthermore, Wnt/ß-catenin signaling pathway might provide a potential explanation for the citrate-stabilized AuNRs-mediated osteogenic differentiation. CONCLUSION: These findings revealed that citrate-stabilized AuNRs with great biocompatibility could regulate the osteogenic differentiation of multiple cell types through Wnt/ß-catenin signaling pathway, which promote innovative AuNRs in the field of tissue engineering and other biomedical applications.

Functionalized Scintillating Nanotubes for Simultaneous Radio- and Photodynamic Therapy of Cancer.

As a model radio-photodynamic therapy (RPDT) agent, we developed a multicomponent nanomaterial by anchoring conjugated chromophores on the surface of scintillating chrysotile nanotubes. Its ultimate composition makes the system a scintillation-activated photosensitizer for the singlet oxygen production. This nanomaterial shows a remarkable ability to enhance the production of singlet oxygen in an aqueous environment, under X-ray irradiation, boosting its production by almost 1 order of magnitude. Its efficiency as a coadjutant for radiotherapy has been tested in vitro, showing a striking efficacy in enhancing both the prompt cytotoxicity of the ionizing radiation and the long-term cytotoxicity given by radiation-activated apoptosis. Notably, the beneficial activity of the RPDT agent is prominent at low levels of delivered doses comparable to the one employed in clinical treatments. This opens the possibility of effectively reducing the therapy exposure and consequently undesired collateral effects due to prolonged exposure of patients to high-energy radiation.

Doxorubicin (DOX) Gadolinium-Gold-Complex: A New Way to Tune Hybrid Nanorods as Theranostic Agent.

INTRODUCTION: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl4) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl3 * 6 H2O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption. MATERIAL AND METHOD: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation. RESULTS: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r1 relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues. CONCLUSION: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T1 features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.

Gold Nanorod-Melanin Hybrids for Enhanced and Prolonged Photoacoustic Imaging in the Near-Infrared-II Window.

Photoacoustic (PA) imaging holds great promise as a noninvasive imaging modality. Gold nanorods (GNRs) with absorption in the second near-infrared (NIR-II) window have emerged as excellent PA probes because of their tunable optical absorption, surface modifiability, and low toxicity. However, pristine GNRs often undergo shape transition upon laser illumination due to thermodynamic instability, leading to a reduced PA signal after a few seconds of imaging. Here, we report monodisperse GNR-melanin nanohybrids where a tunable polydopamine (PDA) coating was conformally coated on GNRs. GNR@PDAs showed a threefold higher PA signal than pristine GNRs due to the increased optical absorption, cross-sectional area, and thermal confinement. More importantly, the PA signal of GNR@PDAs only decreased by 29% during the 5 min of laser illumination in the NIR-II window, while significant attenuation (77%) was observed for GNRs. The GNR@PDAs maintained 87% of its original PA signal in vivo even after 10 min of laser illumination. This PDA-enabled strategy affords a rational design for robust PA imaging probes and provides more opportunities for other types of photomediated biomedicines, such as photothermal and photodynamic regimens.

Pathogenic Stress Induces Human Monocyte to Express an Extracellular Web of Tunneling Nanotubes.

Actin-based tunneling nanotubes are a means of intercellular communication between remote cells. In the last decade, this type of nanotube was described in a wide variety of cell types and it became widely accepted that communication through these nanotubes is related to response to environmental changes. Few reports, however, are available regarding the expression of similar nanotubes in vivo or in primary cells. Moreover, the functional significance of this intercellular communication for health and disease is largely unknown. In this context, and as a first step in unraveling these questions, we examined the formation of similar nanotubes in primary peripheral human monocytes. To that end, we combined the use of a live cell imaging system along with advanced methods of fluorescent and scanning electron microscopy. This experimental approach reveals for the first time that the bacterial lipopolysaccharide endotoxin induces a transient expression of an unexpected abundance of actin-based tunneling nanotubes associated with vesicles. In addition, it was found that a similar response can be achieved by treating human monocytes with various bacterial and yeast membrane components, as well as with a viral component analog. In all these cases, this response is mediated by distinct complexes of toll-like receptors. Therefore, we suggest that the observed phenomena are related to a broad type of monocyte pathogen response, and raise the possibility that the phenomena described above may be involved in many clinical situations related to inflammation as a new topic of study.

Antimicrobial Effect and Cytotoxic Evaluation of Mg-Doped Hydroxyapatite Functionalized with Au-Nano Rods.

Hydroxyapatite (HA) is the main inorganic mineral that constitutes bone matrix and represents the most used biomaterial for bone regeneration. Over the years, it has been demonstrated that HA exhibits good biocompatibility, osteoconductivity, and osteoinductivity both in vitro and in vivo, and can be prepared by synthetic and natural sources via easy fabrication strategies. However, its low antibacterial property and its fragile nature restricts its usage for bone graft applications. In this study we functionalized a MgHA scaffold with gold nanorods (AuNRs) and evaluated its antibacterial effect against S. aureus and E. coli in both suspension and adhesion and its cytotoxicity over time (1 to 24 days). Results show that the AuNRs nano-functionalization improves the antibacterial activity with 100% bacterial reduction after 24 h. The toxicity study, however, indicates a 4.38-fold cell number decrease at 24 days. Although further optimization on nano-functionalization process are needed for cytotoxicity, these data indicated that Au-NRs nano-functionalization is a very promising method for improving the antibacterial properties of HA.