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Anti-RhoJ antibody functionalized Au@I nanoparticles as CT-guided tumor vessel-targeting radiosensitizers in patient-derived tumor xenograft model

Biomaterials - Mon, 2017-06-26 23:58
Publication date: October 2017
Source:Biomaterials, Volume 141

Author(s): Sen Liu, Hui Li, Luyao Xia, Peipei Xu, Yin Ding, Da Huo, Yong Hu

The clinical success of radiotherapy is greatly hampered due to its intolerable off-target cytotoxicity induced by the high dose of radiation. Meanwhile, low dose of irradiation greatly potentiates the intratumoral angiogenesis, which promotes the local relapse and metastasis of tumor. Therefore, it is essential to reduce the irradiation dosage while inhibiting the tumor angiogenesis during radiotherapy. In this work, tumor vessel specific ultrafine Au@I nanoparticles (AIRA NPs) are fabricated and used as targeted radiosensitizers. Due to the presence of Au and iodine, these AIRA NPs exhibit superb X-ray attenuation for contrast-enhanced computed tomography (CT). Once injected, these AIRA NPs bind specifically to both newly formed tumor vessels in peri- and intratumoral regions and pre-existing tumor vessels. Upon radiation under CT guidance, AIRA NPs remarkably enhanced the killing efficacy against tumors in vivo with respect to radiation alone or anti-angiogenesis chemotherapy. Meanwhile, down-regulation of the level of circulating VEGF cytokine further indicates that our strategy can eradicate tumor without risking the recurrence of hypoxia and angiogenesis. Our demonstration provides a robust method of cancer therapy integrating good biocompatibility, high specificity and relapse-free manner alternative to traditional metal NPs enhanced radiotherapy.
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Linker-free covalent immobilization of heparin, SDF-1α, and CD47 on PTFE surface for antithrombogenicity, endothelialization and anti-inflammation

Biomaterials - Mon, 2017-06-26 23:58
Publication date: September 2017
Source:Biomaterials, Volume 140

Author(s): Ang Gao, Ruiqiang Hang, Wan Li, Wei Zhang, Penghui Li, Guomin Wang, Long Bai, Xue-Feng Yu, Huaiyu Wang, Liping Tong, Paul K. Chu

Small-diameter vascular grafts made of biomedical polytetrafluoroethylene (PTFE) suffer from the poor long-term patency rate originating from thrombosis and intimal hyperplasia, which can be ascribed to the insufficient endothelialization and chronic inflammation of the materials. Hence, bio-functionalization of PTFE grafts is highly desirable to circumvent these disadvantages. In this study, a versatile “implantation-incubation” approach in which the biomedical PTFE is initially modified by plasma immersion ion implantation (PIII) is described. After the N2 PIII treatment, the surface of biomedical PTFE is roughened with nanostructures and more importantly, the abundant free radicals generated underneath the surface continuously migrate to the surface and react with environmental molecules. Taking advantage of this mechanism, various biomolecules with different functions can be steadily immobilized on the surface of PTFE by simple solution immersion. As examples, three typical biomolecules, heparin, SDF-1α, and CD47, are covalently grafted onto the PTFE. In addition to retaining the bioactivity, the surface-functionalized PTFE exhibits reduced thrombogenicity, facilitates the recruitment of endothelial progenitor cells, and even alleviates the inflammatory immune responses of monocytes-macrophages and is thus promising to the development of small-diameter prosthetic vascular grafts with good long-term patency.
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Construction of an alkaline phosphatase-specific two-photon probe and its imaging application in living cells and tissues

Biomaterials - Mon, 2017-06-26 23:58
Publication date: September 2017
Source:Biomaterials, Volume 140

Author(s): Huatang Zhang, Peng Xiao, Yin Ting Wong, Wei Shen, Mohit Chhabra, Raoul Peltier, Yin Jiang, Yonghe He, Jun He, Yi Tan, Yusheng Xie, Derek Ho, Yun-Wah Lam, Jinpeng Sun, Hongyan Sun

Alkaline phosphatase (ALP) is a family of enzymes involved in the regulation of important biological processes such as cell differentiation and bone mineralization. Monitoring the activity of ALP in serum can help diagnose a variety of diseases including bone and liver diseases. There has been growing interest in developing new chemical tools for monitoring ALP activity in living systems. Such tools will help further delineate the roles of ALP in biological and pathological processes. Previously reported fluorescent probes has a number of disadvantages that limit their application, such as poor selectivity and short-wavelength excitation. In this work, we report a new two-photon fluorescent probe (TP-Phos) to selectively detect ALP activity. The probe is composed of a two-photon fluorophore, a phosphate recognition moiety, and a self-cleavable adaptor. It offers a number of advantages over previously reported probes, such as fast reaction kinetics, high sensitivity and low cytotoxicity. Experimental results also showed that TP-Phos displayed improved selectivity over DIFMUP, a commonly utilized ALP probe. The selectivity is attributed to the utilization of an ortho-functionalised phenyl phosphate group, which increases the steric hindrance of the probe and the active site of phosphatases. Moreover, the two-photon nature of the probe confers enhanced imaging properties such as increased penetration depth and lower tissue autofluorescence. TP-Phos was successfully used to image the endogenous ALP activity of hippocampus, kidney and liver tissues from rat.





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Fibrillin-2 and Tenascin-C bridge the age gap in lung epithelial regeneration

Biomaterials - Mon, 2017-06-26 23:58
Publication date: September 2017
Source:Biomaterials, Volume 140

Author(s): Sarah E. Gilpin, Qiyao Li, Daniele Evangelista-Leite, Xi Ren, Dieter P. Reinhardt, Brian L. Frey, Harald C. Ott

Organ engineering based on native matrix scaffolds involves combining regenerative cell populations with corresponding biological matrices to form functional grafts on-demand. The extracellular matrix (ECM) that is retained following lung decellularization provides essential structure and biophysical cues for whole organ regeneration after recellularization. The unique ECM composition in the early post-natal lung, during active alveologenesis, may possess distinct signals that aid in driving cell adhesion, survival, and proliferation. We evaluated the behavior of basal epithelial stem cells (BESCs) isolated from adult human lung tissue, when cultured on acellular ECM derived from neonatal (aged < 1 week) or adult lung donors (n = 3 donors per group). A significant difference in cell proliferation and survival was found. We next performed in-depth proteomic analysis of the lung scaffolds to quantify proteins significantly enriched in the neonatal ECM, and identified the glycoproteins Fibrillin-2 (FBN-2) and Tenascin-C (TN-C) as potential mediators of the observed effect. BESCs cultured on Collagen Type IV coated plates, supplemented with FBN-2 and TN-C demonstrated significantly increased proliferation and decreased cellular senescence. No significant increase in epithelial-to-mesenchymal transition was observed. In vitro migration was also increased by FBN-2 and TN-C treatment. Decellularized lung scaffolds treated with FBN-2 and TN-C prior to re-epithelialization supported greater epithelial proliferation and tissue remodeling. BESC distribution, matrix alignment, and overall tissue morphology was improved on treated lung scaffolds, after 3 and 7 days of ex vivo lung culture. These results demonstrate that scaffold re-epithelialization is enhanced on neonatal lung ECM, and that supplementation of FBN-2 and TN-C to the native scaffold may be a valuable tool in lung tissue regeneration.





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Adipose-derived stem cell sheets functionalized by hybrid baculovirus for prolonged GDNF expression and improved nerve regeneration

Biomaterials - Mon, 2017-06-26 23:58
Publication date: September 2017
Source:Biomaterials, Volume 140

Author(s): Mu-Nung Hsu, Han-Tsung Liao, Kuei-Chang Li, Hwei-Hsien Chen, Tzu-Chen Yen, Pavel Makarevich, Yelena Parfyonova, Yu-Chen Hu

Peripheral nerve regeneration requires coordinated functions of supporting cells (e.g. Schwann cells) and neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF), but nerve regeneration is usually far from complete. Here we constructed a Cre/loxP-based hybrid baculovirus (BV) vector which enabled intracellular formation of episomal DNA minicircle for effective transduction of rat adipose-derived stem cells (ASCs) and prolonged expression of functional GDNF capable of recruiting Schwann cells. The GDNF expression persisted for >20 days with the peak level (≈128 ng/ml) tremendously exceeding the picogram levels of GDNF secreted by neuroprogenitor cells. We further developed a facile method to fabricate and transduce cell sheets composed of undifferentiated ASCs in 2 days, without the need of thermo-responsive polymer commonly used for cell sheet fabrication. Implantation of the hybrid BV-engineered, GDNF-expressing ASCs sheets into sciatic nerve transection site in rats significantly improved the nerve repair, as judged from the enhanced functional recovery, nerve reinnervation, electrophysiological functionality, Schwann cells proliferation/infiltration, axon regeneration, myelination and angiogenesis. The hybrid BV is able to functionalize ASCs sheets by intracellular episomal DNA minicircle formation that circumvents undesired gene integration, and the ASCs sheets fabrication is rapid and simple. These data and features implicate the potentials of ASCs sheets functionalized by the hybrid BV for peripheral nerve regeneration.





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Amorphous Metal Polysulfides: Electrode Materials with Unique Insertion/Extraction Reactions

Journal of the American Chemical SocietyDOI: 10.1021/jacs.7b03909
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50th Anniversary Perspective: Polymer Functionalization

Macromolecules - Mon, 2017-06-26 12:23

MacromoleculesDOI: 10.1021/acs.macromol.7b00465
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Depolarized Scattering from Block Copolymer Grains Using Circularly Polarized Light

Macromolecules - Mon, 2017-06-26 12:23

MacromoleculesDOI: 10.1021/acs.macromol.7b01048
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Chirality Control of Electron Transfer in Quantum Dot Assemblies

Journal of the American Chemical SocietyDOI: 10.1021/jacs.7b04639
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Water in Ionic Liquid Lubricants: Friend and Foe

ACS Nano - Mon, 2017-06-26 10:09

ACS NanoDOI: 10.1021/acsnano.7b01835
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Distinct Bimodal Roles of Aromatic Molecules in Controlling Gold Nanorod Growth for Biosensing

Advanced Functional Materials - Mon, 2017-06-26 07:19

New aromatic molecule–seed particle interactions are examined and exploited to control and guide seed-mediated gold nanorod (Au NR) growth. This new approach enables better understanding of how small molecules impact the synthesis of metallic nanostructures, catalyzing their use in various biomedical applications, such as plasmonic biosensing. Experimental studies and theoretical molecular simulations using a library of aromatic molecules, making use of the chemical versatility of the molecules with varied spatial arrangements of electron-donating/withdrawing groups, charge, and Au-binding propensity, are performed. Au NR growth is regulated by two principal mechanisms, producing either a red or blue shift in the longitudinal localized surface plasmon resonance (LLSPR) peaks. Aromatic molecules with high redox potentials produce an increase in NR aspect ratio and red shift of LLSPR peaks. In contrast, molecules that strongly bind gold surfaces result in blue shifts, demonstrating a strong correlation between their binding energy and blue shifts produced. Through enzymatic conversion of selected molecules, 4-aminophenylphosphate to 4-aminophenol, opposing growth mechanisms at opposite extremes of target concentration are obtained, and a chemical pathway for performing plasmonic enzyme-linked immunosorbent assays is established. This unlocks new strategies for tailoring substrate design and enzymatic mechanisms for controlling plasmonic response to target molecules in biosensing applications.

Aromatic molecule–seed particle interactions are introduced as a novel chemical approach to control anisotropic growth of gold nanorods (Au NRs). The interaction of seeds with reducing aromatic molecules produces Au NRs with higher aspect ratios and red-shifted plasmonic peaks, while the interaction with gold surface-binding molecules yields Au NRs with lower aspect ratios and blue-shifted peaks. These observations enable more sophisticated engineering of anisotropic nanoparticle growth.

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Highly Stable Colloidal “Giant” Quantum Dots Sensitized Solar Cells

Advanced Functional Materials - Mon, 2017-06-26 07:13

Colloidal quantum dots (QDs) are widely studied due to their promising optoelectronic properties. This study explores the application of specially designed and synthesized “giant” core/shell CdSe/(CdS)x QDs with variable CdS shell thickness, while keeping the core size at 1.65 nm, as a highly efficient and stable light harvester for QD sensitized solar cells (QDSCs). The comparative study demonstrates that the photovoltaic performance of QDSCs can be significantly enhanced by optimizing the CdS shell thickness. The highest photoconversion efficiency (PCE) of 3.01% is obtained at optimum CdS shell thickness ≈1.96 nm. To further improve the PCE and fully highlight the effect of core/shell QDs interface engineering, a CdSexS1−x interfacial alloyed layer is introduced between CdSe core and CdS shell. The resulting alloyed CdSe/(CdSexS1−x)5/(CdS)1 core/shell QD-based QDSCs yield a maximum PCE of 6.86%, thanks to favorable stepwise electronic band alignment and improved electron transfer rate with the incorporation of CdSexS1−x interfacial layer with respect to CdSe/(CdS)6 core/shell. In addition, QDSCs based on “giant” core/CdS-shell or alloyed core/shell QDs exhibit excellent long-term stability with respect to bare CdSe-based QDSCs. The giant core/shell QDs interface engineering methodology offers a new path to improve PCE and the long-term stability of liquid junction QDSCs.

The “giant” alloyed CdSe/(CdSexS1−x)5/(CdS)1 core/shell quantum dots (QDs) show superior optoelectronic properties, such as broader absorption spectrum, and better carrier separation and transfer rate with respect to CdSe/(CdS)6 core/shell QDs. The alloyed core/shell QDs sensitized solar cells (QDSCs) exhibit a photoconversion efficiency of 6.86% and excellent long-term stability, and offer a new path for liquid junction QDSCs technology.

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Fully-Inkjet-Printed Ag-Coil/NiZn-Ferrite for Flexible Wireless Power Transfer Module: Rigid Sintered Ceramic Body into Flexible Form

Advanced Functional Materials - Sun, 2017-06-25 23:13

Despite the material performances being superior to those of organic materials, inorganic materials are typically excluded for use in flexible and deformable electronic systems because of their rigid nature and the requirement for high processing temperature. This work presents a novel method of utilizing rigid NiZn-ferrite films in a flexible platform and offers an opportunity to realize a flexible wireless power transfer (WPT) module. Inkjet printing is introduced in this study since it can coat NiZn-ferrite films as well as pattern inductor coils for WPTs. A thermochemically inert buffer layer is selected based on a thermodynamic analysis and is introduced as a buffer layer for the NiZn-ferrite to prevent chemical reaction between the ferrite film and the substrate and ensure that the ferrite film can be easily separated from the substrate during a high-temperature sintering process. A Ag-inductor coil is printed on the NiZn-ferrite layer, and then the entire layer is embedded into polydimethylsiloxane, which renders the WPT module flexible. The flexibility of the WPT module is characterized by a bending test, and the structural and magnetic properties are also investigated. The performance of the flexible WPT module is demonstrated by transmitting wireless power to a light emitting diode.

A flexible wireless power transfer (WPT) module is prepared by embedding a Ag-inductor coil/NiZn-ferrite layer into polydimethylsiloxane. This work presents a creative method to utilize a rigid ferrite film in a flexible platform for future flexible electronics. The performance of the flexible WPT module is demonstrated by transmitting a wireless power to a light emitting diode.

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Polymer structure-property requirements for stereolithographic 3D printing of soft tissue engineering scaffolds

Biomaterials - Sat, 2017-06-24 22:49
Publication date: September 2017
Source:Biomaterials, Volume 140

Author(s): Ryan J. Mondschein, Akanksha Kanitkar, Christopher B. Williams, Scott S. Verbridge, Timothy E. Long

This review highlights the synthesis, properties, and advanced applications of synthetic and natural polymers 3D printed using stereolithography for soft tissue engineering applications. Soft tissue scaffolds are of great interest due to the number of musculoskeletal, cardiovascular, and connective tissue injuries and replacements humans face each year. Accurately replacing or repairing these tissues is challenging due to the variation in size, shape, and strength of different types of soft tissue. With advancing processing techniques such as stereolithography, control of scaffold resolution down to the μm scale is achievable along with the ability to customize each fabricated scaffold to match the targeted replacement tissue. Matching the advanced manufacturing technique to polymer properties as well as maintaining the proper chemical, biological, and mechanical properties for tissue replacement is extremely challenging. This review discusses the design of polymers with tailored structure, architecture, and functionality for stereolithography, while maintaining chemical, biological, and mechanical properties to mimic a broad range of soft tissue types.





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Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of EPR effect and albumin-protein interactions using S-nitrosated human serum albumin dimer

Biomaterials - Sat, 2017-06-24 22:49
Publication date: September 2017
Source:Biomaterials, Volume 140

Author(s): Ryo Kinoshita, Yu Ishima, Victor T.G. Chuang, Hideaki Nakamura, Jun Fang, Hiroshi Watanabe, Taro Shimizu, Keiichiro Okuhira, Tatsuhiro Ishida, Hiroshi Maeda, Masaki Otagiri, Toru Maruyama

In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane®). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models. In the high vascular permeability C26 murine colon cancer subcutaneous inoculation model, SNO-HSA Dimer enhanced tumor selectivity of nab-PTX, and attenuated myelosuppression. SNO-HSA Dimer also augmented the tumor growth inhibition of nab-PTX in low vascular permeability B16 murine melanoma subcutaneous inoculation model. Furthermore, nab-PTX therapy combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. In conclusion, SNO-HSA Dimer could enhance the therapeutic effect of nab-PTX even in low vascular permeability or intractable pancreatic cancers. The possible underlying mechanisms of action of SNO-HSA Dimer were discussed.
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