Journal feeds

 

Nitrogen-doped graphene quantum dots (N-GQDs) perturb redox-sensitive system <em>via</em> the selective inhibition of antioxidant enzyme activities in zebrafish

Biomaterials - 3 hours 30 min ago

Publication date: Available online 23 March 2019

Source: Biomaterials

Author(s): Shun Deng, Ailing Fu, Muhammad Junaid, Yan Wang, Qian Yin, Chen Fu, Li Liu, Dong-Sheng Su, Wan-Ping Bian, De-Sheng Pei

Abstract

Graphene quantum dots (GQDs) are well-known for its potential applications for bioimaging, biosensor, and drug carrier in biomedicine. GQDs are well characteristic of intrinsic peroxidase-like catalytic activity, which is proven effective in scavenging the free radicals, such as superoxide anion hydrogen peroxide and hydroxyl radical. GQDs are also well praised for its low in vivo and in vitro toxicity. Here, we found that nitrogen-doped GQDs (N-GQDs) can strongly disturb redox-sensitive system via the selective inhibition of endogenous antioxidant enzyme activities in zebrafish. The enzyme activities or transcription levels of a battery of hemoproteins including catalase (CAT), superoxide dismutase (SOD), respiratory chain complex I, complex Ⅲ, hemoglobin (Hb), and myeloperoxidase (MPO), were significantly suppressed by N-GQDs. We also found that N-GQDs activated the cytochrome P450 monooxygenase (e.g. cyp1a) and the associated aryl-hydrocarbon receptor repressors (ahrr1 and ahrr2) in zebrafish embryos. Compared to the ultrasmall graphene oxide (USGO), N-GQDs exhibited stronger fluorescent permeability and tissue-specific bio-accumulative effects. Taken together, our findings highlighted that exposure to N-GQDs can disrupt endogenous antioxidant enzyme activities, possibly via the competitive inhibition of electron transfer process. Our results in this study provided solid data for biosafety evaluations of various types of GQDs, and created an alert for the future biomedical applications of N-GQDs.

Categories: Journal feeds

Liver fibrosis affects the targeting properties of drug delivery systems to macrophage subsets in vivo

Biomaterials - 3 hours 30 min ago

Publication date: Available online 22 March 2019

Source: Biomaterials

Author(s): Can Ergen, Patricia Niemietz, Felix Heymann, Maike Baues, Felix Gremse, Robert Pola, Louis van Bloois, Gert Storm, Fabian Kiessling, Christian Trautwein, Tom Luedde, Twan Lammers, Frank Tacke

Abstract

Myeloid immune cells promote inflammation and fibrosis in chronic liver diseases. Drug delivery systems, such as polymers, liposomes and microbubbles, efficiently target myeloid cells in healthy liver, but their targeting properties in hepatic fibrosis remain elusive. We therefore studied the biodistribution of three intravenously injected carrier material, i.e. 10 nm poly(N-(2-hydroxypropyl)methacrylamide) polymers, 100 nm PEGylated liposomes and 2000 nm poly(butyl cyanoacrylate) microbubbles, in two fibrosis models in immunocompetent mice. While whole-body imaging confirmed preferential hepatic uptake even after induction of liver fibrosis, flow cytometry and immunofluorescence analysis revealed markedly decreased carrier uptake by liver macrophage subsets in fibrosis, particularly for microbubbles and polymers. Importantly, carrier uptake co-localized with immune infiltrates in fibrotic livers, corroborating the intrinsic ability of the carriers to target myeloid cells in areas of inflammation. Of the tested carrier systems liposomes had the highest uptake efficiency among hepatic myeloid cells, but the lowest specificity for cellular subsets. Hepatic fibrosis affected carrier uptake in liver and partially in spleen, but not in other tissues (blood, bone marrow, lung, kidney). In conclusion, while drug carrier systems target distinct myeloid cell populations in diseased and healthy livers, hepatic fibrosis profoundly affects their targeting efficiency, supporting the need to adapt nanomedicine-based approaches in chronic liver disease.

Categories: Journal feeds

Self‐Powered Distributed Water Level Sensors Based on Liquid–Solid Triboelectric Nanogenerators for Ship Draft Detecting

Advanced Functional Materials - Fri, 2019-03-22 12:41

A self‐powered water level sensor based on liquid–solid tubular triboelectric nanogenerator (LST‐TENG) is proposed and analyzed. It shows that the water level sensor has stable performance for liquid–solid interface monitoring. The ship draft is successfully detected using the LST‐TENG with high accuracy. This LST‐TENG is self‐powered, robust, and accurate for extensive applications in marine industry.


Abstract

Ship draft measurement is of great significance for ensuring navigation safety and facilitating ship control. In this work, a self‐powered water level sensor based on a liquid–solid tubular triboelectric nanogenerator (LST‐TENG) is proposed and analyzed. The LST‐TENG is made of multiple copper electrodes uniformly distributed along a polytetrafluoroethylene (PTFE) tube. When water flows into the PTFE tube, it induces alternating flows of electrons between the main electrode and the distributed bottom electrodes. The obvious peaks in the derivative of open‐circuit voltage with respect to time are found to correspond with the electrode distribution. Then it can be utilized as a robust and sensitive indicator for detecting the water level as the number of obvious peaks in the derivative of open‐circuit voltage is directly related to the water level height. The ship draft is successfully detected using the LST‐TENG with an accuracy of 10 mm. It shows that the water level sensor has stable performance for liquid–solid interface monitoring. Therefore, this LST‐TENG is self‐powered, robust, and accurate for extensive applications in marine industry.

Categories: Journal feeds

Novel Strategy to Accelerate Bone Regeneration of Calcium Phosphate Cement by Incorporating 3D Plotted Poly(lactic‐co‐glycolic acid) Network and Bioactive Wollastonite

Advanced Healthcare Materials - Fri, 2019-03-22 07:29

A calcium phosphate–based composite cement is successfully constructed by infiltrating the cement pastes into a 3D PLGA network prepared by the 3D plotting technique, and in vivo experimental results show that the composites promote fast angiogenesis and bone formation. This modification strategy is expected to facilitate the wider application of calcium phosphate cement in clinic.


Abstract

Inefficient bone regeneration of self‐hardening calcium phosphate cement (CPC) increases the demand for interconnected macropores and osteogenesis‐stimulated substances. It remains a challenge to fabricate porous CPC with interconnected macropores while maintaining its advantages, such as plasticity. Herein, pastes containing CPC and wollastonite (WS) are infiltrated into a 3D plotted poly(lactic‐co‐glycolic acid) (PLGA) network to fabricate plastic CPC‐based composite cement (PLGA/WS/CPC). The PLGA/WS/CPC recovers the plasticity of CPC after being heated above the glass transition temperature of PLGA. The presence of the 3D PLGA network significantly increases the flexibility of CPC in prophase and generates 3D interconnected macropores in situ upon its degradation. The addition of WS is helpful to improve the attachment, proliferation, and osteogenic differentiation of mouse bone marrow stromal cells in vitro. The in vivo experimental results indicate that PLGA/WS/CPC promotes rapid angiogenesis and bone formation. Therefore, the plastic CPC‐based composite cement with a 3D PLGA network and wollastonite shows an obviously improved efficiency for repairing bone defects and is expected to facilitate the wider application of CPC in the clinic.

Categories: Journal feeds

Ultrasound/Acidity‐Triggered and Nanoparticle‐Enabled Analgesia

Advanced Healthcare Materials - Fri, 2019-03-22 07:24

A unique dual stimuli‐responsive (ultrasound and acidity) hollow mesoporous organosilica nanoparticles (HMONs)‐based nanoplatforms, ropivacaine@HMONs, are engineered for achieving on‐demand and long‐lasting pain relief, which are demonstrated by the in vivo mouse model of incision pain. The low neurotoxicity and high biocompatibility of HMONs for nanoparticle‐enabled analgesia are also demonstrated both in vitro and in vivo.


Abstract

Local anesthetics have been extensively employed to treat postoperative pain, but they generally suffer from short acting duration and potential neurotoxicity under high local concentrations, which require the controlled and sustained releasing patterns of treatment drugs. In this work, it is reported, for the first time, the construction of hollow mesoporous organosilica nanoparticles (HMONs)‐based nanoplatforms for localized delivery and controlled/sustained release of loaded ropivacaine for local anesthetics, which can be repeatedly triggered by either external ultrasound irradiation or acidity triggering to release the payload, causing on‐demand and long‐lasting analgesia. Based on the in vivo mouse model of incision pain, the controlled and sustained release of ropivacaine achieves more than six hours of continuous analgesia, which is almost three times longer as compared to single free ropivacaine injection. The low neurotoxicity and high biocompatibility of HMONs for nanoparticle‐enabled analgesia are also demonstrated both in vitro and in vivo. This designed/constructed HMONs‐based nanoplatform provides a potential methodology for clinical pain management via on‐demand and long‐lasting pain relief.

Categories: Journal feeds

Migration and Phenotype Control of Human Dermal Fibroblasts by Electrospun Fibrous Substrates

Advanced Healthcare Materials - Fri, 2019-03-22 07:20

Fibrous substrates with oriented fiber configuration are functional in mediating directional cell migration and fibroblast phenotypic change. Human dermal fibroblasts (HDFs) migrate persistently along the fiber axis on fibrous substrates of aligned configuration. Furthermore, myofibroblastic differentiation of HDFs can be induced by aligned fibers, while this effect can be reversed through the introduction of matricellular protein angiopoietin‐like 4.


Abstract

Electrospun fibrous matrices, mimicking extracellular matrix (ECM) hierarchical structures, are potential scaffolds for wound healing. To design functional scaffolds, it is important to explore the interactions between scaffold topographic features and cellular responses, especially directional migration and phenotypic changes, which are critical functional aspects during wound healing. Here, accelerated and persistent migration of human dermal fibroblasts (HDFs) is observed on fibers with aligned orientation. Furthermore, aligned fibers can induce fibroblast‐to‐myofibroblast differentiation of HDFs. During wound healing, the presence of myofibroblasts advances wound repair by rendering contractile force and ECM deposition within the early and middle courses, but its continuous persistence in the later event may not be desired due to the contribution in pathological scarring. To tune the balance, it is noted in this work that the introduction of matricellular protein angiopoietin‐like 4 (ANGPTL4) is capable of reversing the phenotypic alteration induced by aligned fibers, in a time‐dependent manner. These results indicate fibrous matrices with oriented configuration are functional in mediating directional cell migration and phenotypic change. The discoveries further suggest that tissue‐engineered fibrous grafts with precise alignment modulation and ANGPTL4 releasing properties may thus be promising to promote wound repair with minimizing scar formation.

Categories: Journal feeds

Hypoxia alleviation-triggered enhanced photodynamic therapy in combination with IDO inhibitor for preferable cancer therapy

Biomaterials - Fri, 2019-03-22 05:26

Publication date: Available online 22 March 2019

Source: Biomaterials

Author(s): Lei Xing, Jia-Hui Gong, Yi Wang, Yong Zhu, Zhang-Jian Huang, Jun Zhao, Fei Li, Jian-Hua Wang, Hao Wen, Hu-Lin Jiang

Abstract

Photodynamic therapy (PDT) has attracted growing attention in the field of cancer therapy due to its non-invasive intervention and initiation of antitumor immune responses by use of non-toxic photosensitizers (PS) and topical light irradiation. However, inherent hypoxia and immunosuppression mediated by checkpoints in tumors severally impair the efficacy of PDT and PDT-induced immunity. Herein, a multi-functional nanoplatform is rationally constructed by fluorinated polymer nanoparticle saturated with oxygen in advance, which simultaneously encapsulated PS (Ce6) and an indoleamine 2,3-dioxygenase (IDO) inhibitor (NLG919). In particular, the tumor hypoxic microenvironment is obviously relieved and much more reactive oxygen species (ROS) is generated by fluorinated nanoparticle compared with alkylated polymer nanoparticle as a control in vitro and in vivo, this is mainly because the fluorinated polymers are endowed with high oxygen carrying capacity which also contributed to the relief of hypoxia. Meanwhile, compared to PDT alone, the co-encapsulation of IDO inhibitor and PS can further greatly enhance efficacy for inhibiting the growth of primary and abscopal tumors via enhanced T cell infiltration. This study can provide a convenient and practical strategy for enhancing the therapeutic effect of PDT and relieving immune suppression, in turn affording clinical benefits for cancer treatment.

Categories: Journal feeds

Dissecting hiPSC-CM pacemaker function in a cardiac organoid model

Biomaterials - Fri, 2019-03-22 05:26

Publication date: Available online 21 March 2019

Source: Biomaterials

Author(s): Mirja L. Schulze, Marc D. Lemoine, Alexander W. Fischer, Katharina Scherschel, Robert David, Kristoffer Riecken, Arne Hansen, Thomas Eschenhagen, Bärbel M. Ulmer

Abstract

Biological pacemakers could be a promising alternative to electronic pacemakers and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) may represent a suitable source for implantable cells. To further unravel this potential a thorough understanding of pacemaker function with regard to coupling processes both in the physiological and in the graft-host context is required. Here we developed a 2-component cardiac organoid model with a hiPSC-CM embryoid body (EB) as trigger casted into a rat engineered heart tissue (EHT) as arrhythmic beating substrate. Contractility recordings revealed that the EB controlled the beating activity of the EHT, leading to a regular hiPSC-CM-like beating pattern instead of the irregular beating typically seen in rat EHT. Connectivity was observed with action potential (AP) measurements and calcium transients transmitting from the EB directly into the rat EHT. Immunohistochemistry and genetically labeled hiPS-CMs demonstrated that EB-derived and rat cells intermingled and formed a transitional zone. Connexin 43 expression followed the same pattern as histological and computer models have indicated for the human sinoatrial node. In conclusion, hiPSC-CM EBs function as a biological pacemaker in a 2-component cardiac organoid model, which provides the possibility to study electrophysiological and structural coupling mechanisms underlying propagation of pacemaker activity.

Categories: Journal feeds

Engineering a naturally-derived adhesive and conductive cardiopatch

Biomaterials - Fri, 2019-03-22 05:26

Publication date: Available online 21 March 2019

Source: Biomaterials

Author(s): Brian W. Walker, Roberto Portillo Lara, Chu Yu, Ehsan Shirzaei Sani, William Kimball, Shannon Joyce, Nasim Annabi

Abstract

Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.

Categories: Journal feeds

Bioinspired nanoplatelets for chemo-photothermal therapy of breast cancer metastasis inhibition

Biomaterials - Fri, 2019-03-22 05:26

Publication date: Available online 21 March 2019

Source: Biomaterials

Author(s): Hao Ye, Kaiyuan Wang, Menglin Wang, Rongzheng Liu, Hang Song, Na Li, Qi Lu, Wenjuan Zhang, Yuqian Du, Wenqian Yang, Lu Zhong, Yu Wang, Bohong Yu, Hong Wang, Qiming Kan, Haotian Zhang, Yongjun Wang, Zhonggui He, Jin Sun

Abstract

Breast cancer is associated with high mortality due to tumor metastasis. The anti-metastasis efficacy of photochemotherapy is strictly limited by poor targeting capability with respect to circulating tumor cells (CTCs) in blood and lymph. Herein, we decorate the platelet membrane (PM) on a surface of nanoparticles (NPs), referred to as nanoplatelets. A chemotherapeutic drug, doxorubicin (DOX), and an FDA-approved photothermal agent, indocyanine green (ICG), are co-encapsulated into the biomimetic nanoplatelets. Nanoplatelets possess immune surveillance-escaping capability and specifically capture and clear CTCs in both blood and lymphatic circulations via high-affinity interactions between the P-Selectin of PM and CD44 receptors of tumor cells. PM-coated NPs show greater cellular uptake in MDA-MB-231 breast cancer cells and further elicit higher cytotoxicity to tumor cells relative to uncoated NPs. In vivo, we disclose that the multifunctional nanoplatelets not only completely ablate the primary tumor but also inhibit breast cancer metastasis with high efficiency in the three established xenograft or orthotopic breast tumor-bearing mice models. We conclude that such biomimetic nanoplatelets represent a promising strategy of coating a surface of nanoparticles with platelet membrane to actively capture and destroy CTCs in blood and lymph in breast cancer anti-metastasis therapy.

Categories: Journal feeds

A lanthanide-peptide-derived bacterium-like nanotheranostic with high tumor-targeting, -imaging and -killing properties

Biomaterials - Fri, 2019-03-22 05:26

Publication date: Available online 21 March 2019

Source: Biomaterials

Author(s): Wangxiao He, Jin Yan, Lijuan Wang, Bo Lei, Peng Hou, Wuyuan Lu, Peter X. Ma

Abstract

Nanostructures formed with bioactive peptides offer an exciting prospect in clinical oncology as a novel class of therapeutic agents for human cancers. Despite their therapeutic potential, however, peptide-based nanomedicines are often inefficacious in vivo due to low cargo-loading efficiency, poor tumor cell-targeting specificity and limited drug accumulation in tumor tissues. Here, we describe the design, via assembly of a p53-activating peptide termed PMI, functionalized PEG and fluorescent lanthanide oxyfluoride nanocrystals, of a novel nanotheranostic shaped in flexible rods. This lanthanide-peptide nanorod or LProd of bionic nature exhibited significantly enhanced tumor-targeting and -imaging properties compared to its spherical counterpart. Importantly, LProd potently inhibited tumor growth in a mouse model of human colon cancer through activating tumor suppressor protein p53 via MDM2/MDMX antagonism, while maintaining a highly favorable biosafety profile. Our data demonstrate that LProd as a multifunctional theranostic platform is ideally suited for tumor-specific peptide drug delivery with real-time disease tracking, thereby broadly impacting clinical development of antitumor peptides.

Categories: Journal feeds

[ASAP] Ruthenium-Catalyzed Redox Isomerizations inside Living Cells

Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b00837
Categories: Journal feeds

[ASAP] Control by Metals of Staphylopine Dehydrogenase Activity during Metallophore Biosynthesis

Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b01676
Categories: Journal feeds

[ASAP] a-Ketoesters as Nonaromatic Photoinitiators for Radical Polymerization of (Meth)acrylates

Macromolecules - Thu, 2019-03-21 21:00

MacromoleculesDOI: 10.1021/acs.macromol.8b02640
Categories: Journal feeds

[ASAP] RAFT Dispersion Polymerization in Silicone Oil

Macromolecules - Thu, 2019-03-21 21:00

MacromoleculesDOI: 10.1021/acs.macromol.9b00129
Categories: Journal feeds

Pages