Bio-imaging and Photodynamic Therapy with Tetra Sulphonatophenyl Porphyrin (TSPP)-TiO2 Nanowhiskers: New Approaches in Rheumatoid Arthritis Theranostics.
ABSTRACT: Since Rheumatoid arthritis (RA) is one of the major human joint diseases with unknown etiology, the early diagnosis and treatment of RA remains a challenge. In this contribution we have explored the possibility to utilize novel nanocomposites of tetera suplhonatophenyl porphyrin (TSPP) with titanium dioxide (TiO2) nanowhiskers (TP) as effective bio-imaging and photodynamic therapeutic (PDT) agent for RA theranostics. Our observations demonstrate that TP solution PDT have an ameliorating effect on the RA by decreasing significantly the IL-17 and TNF-? level in blood serum and fluorescent imaging could enable us to diagnose the disease in subclinical stages and bio-mark the RA insulted joint.
Project description:We synthesized superconducting fullerene nanowhiskers (C(60)NWs) by potassium (K) intercalation. They showed large superconducting volume fractions, as high as 80%. The superconducting transition temperature at 17 K was independent of the K content (x) in the range between 1.6 and 6.0 in K-doped C(60) nanowhiskers (K(x)C(60)NWs), while the superconducting volume fractions changed with x. The highest shielding fraction of a full shielding volume was observed in the material of K(3.3)C(60)NW by heating at 200 °C. On the other hand, that of a K-doped fullerene (K-C(60)) crystal was less than 1%. We report the superconducting behaviors of our newly synthesized K(x)C(60)NWs in comparison to those of K(x)C(60) crystals, which show superconductivity at 19 K in K(3)C(60). The lattice structures are also discussed, based on the x-ray diffraction (XRD) analyses.
Project description:The considerable morbidity associated with hospitalized patients and clinics in developed countries due to biofilm formation on biomedical implants and surgical instruments is a heavy economic burden. An alternative to chemically treated surfaces for bactericidal activity started emerging from micro/nanoscale topographical cues in the last decade. Here, we demonstrate a putative antibacterial surface using copper nanowhiskers deposited by molecular beam epitaxy. Furthermore, the control of biological response is based on hydrophobic pinning of water droplets in the Wenzel regime, causing mechanical injury and cell death. Scanning electron microscopy images revealed the details of the surface morphology and non-contact mode laser scanning of the surface revealed the microtopography-associated quantitative parameters. Introducing the bacterial culture over nanowhiskers produces mechanical injury to cells, leading to a reduction in cell density over time due to local pinning of culture medium to whisker surfaces. Extended culture to 72 hours to observe biofilm formation revealed biofilm inhibition with scattered microcolonies and significantly reduced biovolume on nanowhiskers. Therefore, surfaces patterned with copper nanowhiskers can serve as potential antibiofilm surfaces. The topography-based antibacterial surfaces introduce a novel prospect in developing mechanoresponsive nanobiomaterials to reduce the risk of medical device biofilm-associated infections, contrary to chemical leaching of copper as a traditional bactericidal agent.
Project description:Controlled plastic forming of nanoscale metallic objects by applying mechanical load is a challenge, since defect-free nanocrystals usually yield at near theoretical shear strength, followed by stochastic dislocation avalanches that lead to catastrophic failure or irregular, uncontrolled shapes. Herein, instead of mechanical load, we utilize chemical stress from imbalanced interdiffusion to manipulate the shape of nanowhiskers. Bimetallic Au-Fe nanowhiskers with an ultrahigh bending strength were synthesized employing the molecular beam epitaxy technique. The one-sided Fe coating on the defect-free, single-crystalline Au nanowhisker exhibited both single- and polycrystalline regions. Annealing the bimetallic nanowhiskers at elevated temperatures led to gradual change of curvature and irreversible bending. At low homological temperatures at which grain boundary diffusion is a dominant mode of mass transport this irreversible bending was attributed to the grain boundary Kirkendall effect during the diffusion of Au along the grain boundaries in the Fe layer. At higher temperatures and longer annealing times, the bending was dominated by intensive bulk diffusion of Fe into the Au nanowhisker, accompanied by a significant migration of the Au-Fe interphase boundary toward the Fe layers. The irreversible bending was caused by the concentration dependence of the lattice parameter of the Au(Fe) alloy and by the volume effect associated with the interphase boundary migration. The results of this study demonstrate a high potential of chemical interdiffusion in the controlled plastic forming of ultrastrong metal nanostructures. By design of the thickness, microstructure, and composition of the coating as well as the parameters of heat treatment, bimetallic nanowhiskers can be bent in a controlled manner.
Project description:This study describes a class of cellulosic nanomaterials, cellulosic nanowhiskers (CNWs), and demonstrates scaled-up production with acid recovery using less expensive equipment made of common stainless steel rather than glass-lined steel. CNWs produced using concentrated maleic acid (MA) hydrolysis followed by mechanical fibrillation have morphology similar to MA-produced cellulose nanocrystals (CNCs) and sulfuric-acid-produced CNCs (S-CNCs) but differ in crystallinity. Applications of CNWs as a substitute for CNCs for which morphology and surface charge, rather than crystallinity, are the pertinent characteristics are presented. The tested CNW suspensions have a wider viscosity range of 0.001 to 1000 Pa.s over a variety of shear rates of 0.01 to 1000 1/s compared to S-CNCs of 0.001 to 0.1 Pa.s and are better suited for applications such as rheology modification and 3D printing. This study proposes CNWs as a less expensive and sustainable replacement for CNCs in applications that do not require crystalline properties.
Project description:Triptolide (TP), an active component isolated from Tripterygiumwilfordii Hook F, has therapeutic potential against rheumatoid arthritis (RA). However, the underlying molecular mechanism has not been fully elucidated. The aim of this study is to investigate the mechanisms of TP acting on RA by combining bioinformatics analysis with experiment validation. The human protein targets of TP and the human genes of RA were found in the PubChem database and NCBI, respectively. These two dataset were then imported into Ingenuity Pathway Analysis (IPA) software online, and then the molecular network of TP on RA could be set up and analyzed. After that, both in vitro and in vivo experiments were done to further verify the prediction. The results indicated that the main canonical signal pathways of TP protein targets networks were mainly centered on cytokine and cellular immune signaling, and triggering receptors expressed on myeloid cells (TREM)-1 signaling was searched to be the top one shared signaling pathway and involved in the cytokine and cellular immune signaling. Further in vitro experiments indicated that TP not only remarkably lowered the levels of TREM-1 and DNAX-associated protein (DAP)12, but also significantly suppressed the activation of janus activating kinase (JAK)2 and signal transducers and activators of transcription (STAT)3. The expression of tumor necrosis factor (TNF)-?, interleukin (IL)-1? and IL-6 in lipopolysaccharides (LPS)-stimulated U937 cells also decreased after treatment with TP. Furthermore, TREM-1 knockdown was able to interfere with the inhibition effects of TP on these cytokines production. In vivo experiments showed that TP not only significantly inhibited the TREM-1 mRNA and DAP12 mRNA expression, and activation of JAK2 and STAT3 in ankle of rats with collagen-induced arthritis (CIA), but also remarkably decreased production of TNF-?, IL-1? and IL-6 in serum and joint. These findings demonstrated that TP could modulate the TREM1 signal pathway to inhibit the inflammatory response in RA.
Project description:This work reports a newly designed pH-activatable and aniline-substituted aza-boron-dipyrromethene as a trifunctional photosensitizer to achieve highly selective tumor imaging, efficient photodynamic therapy (PDT) and therapeutic self-monitoring through encapsulation in a cRGD-functionalized nanomicelle. The diethylaminophenyl is introduced in to the structure for pH-activatable near-infrared fluorescence and singlet oxygen (1O2) generation, and bromophenyl is imported to increase the 1O2 generation efficiency upon pH activation by virtue of its heavy atom effect. After encapsulation, the nanoprobe can target ?v?3 integrin-rich tumor cells via cRGD and is activated by physiologically acidic pH for cancer discrimination and PDT. The fascinating advantage of the nanoprobe is near-infrared implementation beyond 800 nm, which significantly improves the imaging sensitivity and increases the penetration depth of the PDT. By monitoring the fluorescence decrease in the tumor region after PDT, the therapeutic efficacy is demonstrated in situ and in real time, which provides a valuable and convenient self-feedback function for PDT efficacy tracking. Therefore, this rationally designed and carefully engineered nanoprobe offers a new paradigm for precise tumor theranostics and may provide novel opportunities for future clinical cancer treatment.
Project description:Elevated nitric oxide (NO) levels perform an important pathological role in various inflammatory diseases. Developing NO-activatable theranostic materials with a two-photon excitation (TPE) feature is highly promising for precision imaging and therapy, but constructing such materials is still a tremendous challenge. Here, we present the first example of a NO-activatable fluorescent photosensitizer (DBB-NO) accompanying extremely NO-elevated two-photon absorption (TPA) for efficient fluorescence imaging and photodynamic therapy (PDT). Upon responding to NO, DBB-NO shows not only a remarkably enhanced fluorescence quantum yield (?F, 0.17% vs. 9.3%) and singlet oxygen quantum yield (??, 1.2% vs. 82%) but also an extremely elevated TPA cross-section (?, 270 vs. 2800 GM). Simultaneous enhancement of ??, ?F and ? allows unprecedented two-photon fluorescence brightness (? × ?F = 260.4 GM) and two-photon PDT (TP-PDT) efficiency (? × ?? = 2296 GM) which precedes the value for a commercial two-photon photosensitizer by two orders of magnitude. With these merits, the proof-of-concept applications of NO-activatable two-photon fluorescence imaging and TP-PDT in activated macrophages (in which NO is overproduced) were readily realized. This work may open up many opportunities for constructing two-photon theranostic materials with other pathological condition-activatable features for precise theranostics.
Project description:The manuscript describes the characterization of the interaction between meso-tetrakis(p-sulfonatophenyl)porphyrin (TSPP) and human serum albumin (HSA). TSPP is a candidate for the photosensitization of structural and functional changes in proteins while HSA provides both an excellent protein model and binding and functional characteristics that could be explored in future applications of the approach. A combination of optical spectroscopic techniques (e.g., fluorescence spectroscopy, fluorescence lifetime, circular dichroism, etc.) and computational docking simulations were applied to better characterize the TSPP/HSA interaction. Recent advances have revealed that the complex formed by TSPP and HSA has become potentially relevant to biomedical applications, biomaterials research and protein photosensitized engineering. The study has determined a likely location of the binding site that places TSPP at a site that overlaps partially with the low affinity site of ibuprofen and places one of the [Formula: see text] groups of the ligand in proximity of the Trp214 residue in HSA. The characterization will enable future studies aimed at photosensitizing non-native functions of HSA for biomedical and biomaterial applications.
Project description:TSPP is an anticancer poly-epitope peptide vaccine to thymidylate synthase, recently investigated in the multi-arm phase Ib TSPP/VAC1 trial. TSPP vaccination induced immune-biological effects and showed antitumor activity in metastatic colorectal cancer (mCRC) patients and other malignancies. Progression-free and overall survival of 41 mCRC patients enrolled in the study correlated with baseline levels of CEA, immune-inflammatory markers (neutrophil/lymphocyte ratio, CRP, ESR, LDH, ENA), IL-4 and with post-treatment change in p-ANCA and CD56dimCD16brightNKs (p < 0.04). A subset of 19 patients with activating k-ras mutations showed a different immune-inflammatory response to TSPP as compared to patients with k-ras/wt and a worse outcome in term of PFS (p = 0.048). In patients with k-ras/mut, inflammatory markers lost their predictive value and their survival directly correlated with the baseline levels of IL17/A over the median value (p = 0.01). These results provide strong hints for the design of further clinical trials aimed to test TSPP vaccination in mCRC patients.
Project description:It is essential to develop a novel and versatile strategy for constructing electrically conductive adhesives (ECAs) that have superior conductivity and high mechanical properties. In this work, easily synthesized polyaniline@cellulose (PANI@CNs) nanowhiskers with a high aspect ratio and excellent solubility in 1,4-dioxane were prepared and added to conventional Ag-containing adhesives. A small amount of PANI@CNs can dramatically tune the structure of the ECAs' conductive network and significantly improve the conductivity of the ECAs. Good solubility of PANI@CNs in solvents brings excellent dispersion in the polymer matrix. Thus, a three-dimensional (3D) conducting network formed with dispersed PANI@CNs and Ag flakes can enhance the conductivity of ECAs. The conductivity of the ECAs (with 1.5 wt% PANI@CNs and 55 wt% Ag flakes) showed three orders of magnitude higher than that of the ECAs filled with 55 wt% Ag flakes and 65 wt% Ag flakes. Meanwhile, the integration of PANI@CNs with Ag flakes in polymer matrices also significantly enhanced the mechanical compliance of the resulted ECAs. The resistivity remained unchanged after rolling the PANI@CNs-containing ECAs' film into a 4 mm bending radius for over 1500 cycles. A bendable printed circuit was fabricated using the above PANI@CNs-containing ECAs, which demonstrated their future potential in the field of flexible electronics.