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Rejuvenated Photodynamic Therapy for Bacterial Infections

Advanced Healthcare Materials - 6 hours 17 min ago

Photodynamic antibacterial therapy (PDAT): Owing to its noninvasive nature, broad antibacterial spectrum, and low drug resistance, photodynamic antibacterial therapy has been studied as one of the promising infectious treatments. In this review, the recent development of antibacterial photosensitizers and multifunctional PDAT systems to overcome the inherent defects of PDAT in vivo are summarized in detail.


Abstract

The emergence of multidrug resistant bacterial strains has hastened the exploration of advanced microbicides and antibacterial techniques. Photodynamic antibacterial therapy (PDAT), an old‐fashioned technique, has been rejuvenated to combat “superbugs” and biofilm‐associated infections owing to its excellent characteristics of noninvasiveness and broad antibacterial spectrum. More importantly, bacteria are less likely to produce drug resistance to PDAT because it does not require specific targeting interaction between photosensitizers (PSs) and bacteria. This review mainly focuses on recent developments and future prospects of PDAT. The mechanisms of PDAT against bacteria and biofilms are briefly introduced. In addition to classical macrocyclic PSs, several innovative PSs, including non‐self‐quenching PSs, conjugated polymer–based PSs, and nano‐PSs, are summarized in detail. Numerous multifunctional PDAT systems such as in situ light‐activated PDAT, stimuli‐responsive PDAT, oxygen self‐enriching enhanced PDAT, and PDAT‐based multimodal therapy are highlighted to overcome the inherent defects of PDAT in vivo (e.g., limited penetration depth of light and hypoxic environment of infectious sites).

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A Chitosan–Carbon Nanotube‐Modified Microelectrode for In Situ Detection of Blood Levels of the Antipsychotic Clozapine in a Finger‐Pricked Sample Volume

Advanced Healthcare Materials - 6 hours 18 min ago

A point‐of‐care testing microdevice is developed for antipsychotic clozapine detection in finger‐pricked whole blood. Chitosan–carbon nanotube film is selectively electrodeposited onto a microelectrode and increases the electrochemical current generated by clozapine in the presence of interfering molecules. The study shows, for the first time, the successful detection of clozapine below the clinical threshold in undiluted serum and whole blood.


Abstract

The antipsychotic clozapine is the most effective medication available for schizophrenia and it is the only antipsychotic with a known efficacious clinical range. However, it is dramatically underutilized due to the inability to test clozapine blood levels in finger‐pricked patients' samples. This prevents obtaining immediate blood levels information, resulting in suboptimal treatment. The development of an electrochemical microsensor is presented, which enables, for the first time, clozapine detection in microliters volume whole blood. The sensor is based on a microelectrode modified with micrometer‐thick biopolymer chitosan encapsulating carbon nanotubes. The developed sensor detects clozapine oxidation current, in the presence of other electroactive species in the blood, which generate overlapping electrochemical signals. Clozapine detection, characterized in whole blood from healthy volunteers, displays a sensitivity of 32 ± 3.0 µA cm−2 µmol−1 L and a limit‐of‐detection of 0.5 ± 0.03 µmol L−1. Finally, the developed sensor displays a reproducible electrochemical signal (0.6% relative standard deviation) and high storage stability (9.8% relative standard deviation after 8 days) in serum samples and high repeatability (9% relative standard deviation for the 5th repetition) in whole blood samples. By enabling the rapid and minimally invasive clozapine detection at the point‐of‐care, an optimal schizophrenia treatment is provided.

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In vivo cancer targeting via glycopolyester nanoparticle mediated metabolic cell labeling followed by click reaction

Biomaterials - Tue, 2019-06-25 06:19

Publication date: Available online 25 June 2019

Source: Biomaterials

Author(s): Hua Wang, Yang Bo, Yang Liu, Ming Xu, Kaimin Cai, Ruibo Wang, Jianjun Cheng

Abstract

We developed glycopolyesters (GPs) via azido-sugar initiated ring-opening polymerization of O-carboxyanhydrides (OCAs) and achieved efficient in vivo cancer targeting via GP-nanoparticle (GP-NP) mediated metabolic cell labeling followed by Click reaction. GP-NP shows controlled release of azido-sugars and can efficiently label LS174T colon cancer cells with azido groups in tumor-bearing mice. The exogenously introduced azido groups render excellent in vivo cancer targeting and retention of dibenzocyclooctyne-Cy5 (DBCO-Cy5) with an increasing tumor retention enhancement over time (68% at 6 h, 105% at 24 h, and 191% at 48 h) compared to control mice without azido labeling. The tumor accumulation of DBCO-doxorubicin is also significantly enhanced in GP-NP pretreated mice, resulting in improved in vivo anticancer efficacy. This study, for the first time, proposes the use of azido-sugar initiated polymerization of OCAs to form sugar delivery vehicles with high stability and controlled release, and demonstrates the increasing tumor targeting effect of DBCO-cargo over time by azido-modified tumor cells.

Graphical abstract

Efficient cancel labelling with azido groups was attained by treating mice with azido-sugar conjugated glycopolyester nanoparticles; significantly enhanced targeting and retention of DBCO-cargo in cancer tissues was achieved.

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Semiconducting polymer nanotheranostics for NIR-II/Photoacoustic imaging-guided photothermal initiated nitric oxide/photothermal therapy

Biomaterials - Tue, 2019-06-25 06:19

Publication date: Available online 25 June 2019

Source: Biomaterials

Author(s): Jie Li, Rongcui Jiang, Qi Wang, Xiang Li, Xiaoming Hu, Yan Yuan, Xiaomei Lu, Wenjun Wang, Wei Huang, Quli Fan

Abstract

Gasotransmitters with their cytotoxicity in high concentration have become the focus of attention. For such concentration depended therapy, how to effectively deliver gases and precisely control gases release to the lesion as well as combine them with other therapy to achieve precise therapeutics is still a big challenge. Herein, we realize single near-infrared (NIR) laser-initiated nitric oxide (NO) therapy/photothermal therapy (PTT) using semiconducting polymer nanoparticles (SPNs, PFTDPP) combing s-nitrosothiol groups (the NO donor, SNAP). By the good photothermal conversion effect of SPNs, NIR laser energy can be spatio-temporally controlled to convert into heat to decompose s-nitrosothiol. Meanwhile, considering the accompanied PTT produced by photothermal, we can easily and precisely conduct a dual therapy (NO therapy/PTT) under single NIR laser irradiation. Additionally, semiconducting polymer with its structural modifiability and spectral adjustability can provide a second NIR window & photoacoustic (NIR II/PA) imaging for guiding photothermal initiated NO/photothermal therapy. PFTDPP showed a high photothermal conversion efficiency of 48% and good dual-mode imaging signals (NIR-II/photoacoustic). Cellular test illustrated that NO combined photothermal presented more prominent cytotoxicity than any one of them individually. As the tumor pinpointed in vivo by dual-mode imaging (NIR II/PA), this nanotheranostics provided a tumor inhibition of 77%. Consequently, such phototheranostics produced a new design thought for effectively deliver and precisely controlled release of drugs for oncology. And also, it expanded the application range of gasotransmitters combined therapy that shall have a promising application foreground.

Graphical abstract

Semiconducting Polymer Nanotheranostics can generate heat which then induce the release of nitric oxide under near-infrared laser irradiation. Heat and nitric oxide can produce their corresponding therapy mode to breast cancer. And the Semiconducting polymer can produce its unique imaging property on tumors (a dual-mode imaging signals). Thus, this nanotheranostics produces a dual-mode imaging guided dual-mode therapy.

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Mitigation of monocyte driven thrombosis on cobalt chrome surfaces in contact with whole blood by thin film polar/hydrophobic/ionic polyurethane coatings

Biomaterials - Tue, 2019-06-25 06:19

Publication date: Available online 25 June 2019

Source: Biomaterials

Author(s): Audrey Gossart, Didier Letourneur, Adeline Gand, Véronique Regnault, Mohamed Amine Ben Mlouka, Pascal Cosette, Emmanuel Pauthe, Véronique Ollivier, J. Paul Santerre

Abstract

Monocytes are at the crossroads between inflammation and coagulation processes since they can secrete pro-inflammatory cytokines and express tissue factor (TF), a major initiator of coagulation. Cobalt-chrome (CoCr), a metal alloy, used as a biomaterial for vascular stents, has been shown to be potentially pro-thrombotic and pro-inflammatory. Research work with family of degradable-polar hydrophobic ionic polyurethanes (D-PHI), call HHHI, has been shown to exhibit anti-inflammatory responses from human monocytes. We have generated here multifunctional polyurethane thin films (MPTF) based on the HHHI chemistry as thin coating for CoCr and have evaluated the reactivity of blood with MPTF-coated CoCr. The results showed that the coating of CoCr with MPTF derived from HHHI prevents thrombin generation, reduces coagulation activation, and suppresses fibrin formation in whole blood. Activation of monocytes was also suppressed at the surface of MPTF-coated CoCr and specifically the decrease in thrombin generation was accompanied by a significant decrease in TF and pro-inflammatory cytokine levels. Mass spectroscopy of the adsorbed proteins showed lower levels of fibrinogen, fibronectin and complement C3, C4, and C8 when compared to CoCr. We can conclude that MPTFs reduce the pro-thrombotic and pro-inflammatory phenotype of monocytes and macrophages on CoCr, and prevented clotting in whole blood.

Graphical abstract

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A carrier-free multiplexed gene editing system applicable for suspension cells

Biomaterials - Tue, 2019-06-25 06:19

Publication date: Available online 25 June 2019

Source: Biomaterials

Author(s): Anna Ju, SungWon Lee, Young Eun Lee, Ki-Cheol Han, Jin-Chul Kim, Sang Chul Shin, Hyun Jung Park, Eunice EunKyeong Kim, Seokmann Hong, Mihue Jang

Abstract

Genetically engineered cells via CRISPR/Cas9 system can serve as powerful sources for cancer immunotherapeutic applications. Furthermore, multiple genetic alterations are necessary to overcome tumor-induced immune-suppressive mechanisms. However, one of the major obstacles is the technical difficulty with efficient multiple gene manipulation of suspension cells due to the low transfection efficacy. Herein, we established a carrier-free multiplexed gene-editing platform in a simplified method, which can enhance the function of cytotoxic CD8+ T cells by modulating suspension cancer cells. Our multiple Cas9 ribonucleoproteins (RNPs) enable simultaneous disruption of two programmed cell death 1 (PD-1) ligands, functioning as negative regulators in the immune system, by accessing engineered Cas9 proteins with abilities of complexation and cellular penetration. In addition, combination with electroporation enhanced multiple gene editing efficacy, compared with that by treatment of multiple Cas9 RNPs alone. This procedure resulted in high gene editing at multiple loci of suspension cells. The treatment of multiple Cas9 RNPs targeting both ligands strongly improved Th1-type cytokine production of cytotoxic CD8+ T cells, resulting in synergistic cytotoxic effects against cancer. Simultaneous suppression of PD-L1 and PD-L2 on cancer cells via our developed editing system allows effective antitumor immunity. Furthermore, the treatment of multiple Cas9 RNPs targeting PD-L1, PD-L2, and TIM-3 had approximately 70–90% deletion efficacy. Thus, our multiplexed gene-editing strategy endows potential clinical utilities in cancer immunotherapy.

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<em>In situ</em> repurposing of dendritic cells with CRISPR/Cas9-based nanomedicine to induce transplant tolerance

Biomaterials - Tue, 2019-06-25 06:19

Publication date: Available online 24 June 2019

Source: Biomaterials

Author(s): Yue Zhang, Song Shen, Gui Zhao, Cong-Fei Xu, Hou-Bing Zhang, Ying-Li Luo, Zhi-Ting Cao, Jia Shi, Zhi-Bin Zhao, Zhe-Xiong Lian, Jun Wang

Abstract

Organ transplantation is the only effective method to treat end-stage organ failure. However, it is continuously plagued by immune rejection, which is mostly caused by T cell-mediated reactions. Dendritic cells (DCs) are professional antigen-presenting cells, and blocking the costimulatory signaling molecule CD40 in DCs inhibits T cell activation and induces transplant tolerance. In this study, to relieve graft rejection, Cas9 mRNA (mCas9) and a guide RNA targeting the costimulatory molecule CD40 (gCD40) were prepared and encapsulated into poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-b-PLGA)-based cationic lipid-assisted nanoparticles (CLAN), denoted CLANmCas9/gCD40. CLAN effectively delivered mCas9/gCD40 into DCs and disrupted CD40 in DCs at the genomic level both in vitro and in vivo. After intravenous injection into an acute mouse skin transplant model, CLANmCas9/gCD40-mediated CD40 disruption significantly inhibited T cell activation, which reduced graft damage and prolonged graft survival. This work provides a promising strategy for reprogramming DCs with nanoparticles carrying the CRISPR/Cas9 system to abate transplant rejection.

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Masthead: (Adv. Funct. Mater. 26/2019)

Advanced Functional Materials - Tue, 2019-06-25 02:32
Advanced Functional Materials, Volume 29, Issue 26, June 27, 2019.
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Contents: (Adv. Funct. Mater. 26/2019)

Advanced Functional Materials - Tue, 2019-06-25 02:32
Advanced Functional Materials, Volume 29, Issue 26, June 27, 2019.
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Stem Cell Immunotherapy: Local Immune‐Triggered Surface‐Modified Stem Cells for Solid Tumor Immunotherapy (Adv. Funct. Mater. 26/2019)

Advanced Functional Materials - Tue, 2019-06-25 02:32

In article number https://doi.org/10.1002/adfm.2019007731900773, Kun Na and co‐workers report photosensitizer‐labeled human mesenchymal stem cells (hMSCs‐DPP). The hMSCs‐DPP recognize and migrate towards the cancer. When light is irradiated over the cancerous area, the hMSCs are killed by reactive oxygen species and various cytokines are secreted, and T cells, NK cells, and APC cells accumulate inside the tumors to treat the tumors.


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Flexible Electronics: Tailoring of Silver Nanocubes with Optimized Localized Surface Plasmon in a Gap Mode for a Flexible MoS2 Photodetector (Adv. Funct. Mater. 26/2019)

Advanced Functional Materials - Tue, 2019-06-25 02:32

In article number https://doi.org/10.1002/adfm.2019005411900541, Guanglan Liao and co‐workers report a plasma‐enhanced flexible MoS2 photodetector via the combination of Ag nanocubes and a Ag film underneath. The plasmon intensity is about four orders of magnitude higher than that of Ag nanospheres and nanorods. The flexible MoS2 photodetector exhibits excellent performance (7940 A W−1) at a low operating potential and good mechanical endurance during 10,000 bending cycles.


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Wetting Defects: Simultaneous Detection and Repair of Wetting Defects in Superhydrophobic Coatings via Cassie–Wenzel Transitions of Liquid Marbles (Adv. Funct. Mater. 26/2019)

Advanced Functional Materials - Tue, 2019-06-25 02:32

Damage of superhydrophobic coatings is inevitable despite improvements in mechanical durability and/or self‐healing. In article number https://doi.org/10.1002/adfm.2019006881900688, Mizuki Tenjimbayashi, Masanobu Naito, and Sadaki Samitsu demonstrate a system of simultaneous detection and repair of damaged surface areas using the wetting transition phenomenon of liquid marbles. In this system, the liquid marble recovers the surface wettability in response to wetting defects, which enables sustainable material interfaces.


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Perovskite Nanopatterning: Highly Photoluminescent and Environmentally Stable Perovskite Nanocrystals Templated in Thin Self‐Assembled Block Copolymer Films (Adv. Funct. Mater. 26/2019)

Advanced Functional Materials - Tue, 2019-06-25 02:32

In article number https://doi.org/10.1002/adfm.2018081931808193, Cheolmin Park and co‐workers develop nanostructured organic‐inorganic halide perovskite films via controlled crystallization of the perovskites templated with a self‐assembled block copolymer, one of the most promising bottom‐up processes. The nanopatterned perovskite films of various shapes and nanodomain sizes show excellent photoluminescence with significantly enhanced heat and humidity resistance, making them suitable as color conversion layers for cool‐white emission.


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Proteomics: Nanomaterials in Proteomics (Adv. Funct. Mater. 26/2019)

Advanced Functional Materials - Tue, 2019-06-25 02:32

In article number https://doi.org/10.1002/adfm.2019002531900253, Chunhui Deng and co‐workers focus on the recent design and preparation of nanomaterials with specific recognition ability, as well as their applications in proteomics.


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[ASAP] Micrometer-Sized Water Droplets Induce Spontaneous Reduction

Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b03227
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[ASAP] Mechanisms of Nucleation and Stationary States of Electrochemically Generated Nanobubbles

Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b04479
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[ASAP] A Flexible Microsupercapacitor with Integral Photocatalytic Fuel Cell for Self-Charging

ACS Nano - Mon, 2019-06-24 21:00

ACS NanoDOI: 10.1021/acsnano.9b03603
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[ASAP] Triggered RNAi Therapy Using Metal Inorganic Nanovectors

Molecular Pharmaceutics - Mon, 2019-06-24 21:00

Molecular PharmaceuticsDOI: 10.1021/acs.molpharmaceut.9b00021
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