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Robert Langer

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https://www.readbyqxmd.com/read/29317618/development-of-an-oral-once-weekly-drug-delivery-system-for-hiv-antiretroviral-therapy
#1
Ameya R Kirtane, Omar Abouzid, Daniel Minahan, Taylor Bensel, Alison L Hill, Christian Selinger, Anna Bershteyn, Morgan Craig, Shirley S Mo, Hormoz Mazdiyasni, Cody Cleveland, Jaimie Rogner, Young-Ah Lucy Lee, Lucas Booth, Farhad Javid, Sarah J Wu, Tyler Grant, Andrew M Bellinger, Boris Nikolic, Alison Hayward, Lowell Wood, Philip A Eckhoff, Martin A Nowak, Robert Langer, Giovanni Traverso
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29290812/circulating-magnetic-microbubbles-for-localized-real-time-control-of-drug-delivery-by-ultrasonography-guided-magnetic-targeting-and-ultrasound
#2
Beata Chertok, Robert Langer
Image-guided and target-selective modulation of drug delivery by external physical triggers at the site of pathology has the potential to enable tailored control of drug targeting. Magnetic microbubbles that are responsive to magnetic and acoustic modulation and visible to ultrasonography have been proposed as a means to realize this drug targeting strategy. To comply with this strategy in vivo, magnetic microbubbles must circulate systemically and evade deposition in pulmonary capillaries, while also preserving magnetic and acoustic activities in circulation over time...
2018: Theranostics
https://www.readbyqxmd.com/read/29244511/molecular-rotors-for-universal-quantitation-of-nanoscale-hydrophobic-interfaces-in-microplate-format
#3
Paul William Bisso, Michelle Tai, Hari Katepalli, Nicolas Bertrand, Daniel Blankschtein, Robert Langer
Hydrophobic self-assembly pairs diverse chemical precursors and simple formulation processes to access a vast array of functional colloids. Exploration of this design space, however, is stymied by lack of broadly general, high-throughput colloid characterization tools. Here, we show that a narrow structural subset of fluorescent, zwitterionic molecular rotors - dialkylaminostilbazolium sulfonates [DASS] with intermediate-length alkyl tails - fills this major analytical void by quantitatively sensing hydrophobic interfaces in microplate format...
December 15, 2017: Nano Letters
https://www.readbyqxmd.com/read/29220013/corrigendum-in-vivo-genome-editing-and-organoid-transplantation-models-of-colorectal-cancer-and-metastasis
#4
Jatin Roper, Tuomas Tammela, Naniye Malli Cetinbas, Adam Akkad, Ali Roghanian, Steffen Rickelt, Mohammad Almeqdadi, Katherine Wu, Matthias A Oberli, Francisco Sánchez-Rivera, Yoona K Park, Xu Liang, George Eng, Martin S Taylor, Roxana Azimi, Dmitriy Kedrin, Rachit Neupane, Semir Beyaz, Ewa T Sicinska, Yvelisse Suarez, James Yoo, Lillian Chen, Lawrence Zukerberg, Pekka Katajisto, Vikram Deshpande, Adam J Bass, Philip N Tsichlis, Jacqueline Lees, Robert Langer, Richard O Hynes, Jianzhu Chen, Arjun Bhutkar, Tyler Jacks, Ömer H Yilmaz
This corrects the article DOI: 10.1038/nbt.3836.
December 8, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29191009/prediction-of-broad-spectrum-pathogen-attachment-to-coating-materials-for-biomedical-devices
#5
Paulius Mikulskis, Andrew L Hook, Adam Dundas, Derek J Irvine, Olutoba Sanni, Daniel G Anderson, Robert Langer, Morgan Russell Alexander, Paul Williams, David A Winkler
Bacterial infections in healthcare settings are a frequent accompaniment to both routine procedures such as catheterization and surgical site interventions. Their impact is becoming even more marked as the numbers of medical devices that are used to manage chronic health conditions and improve quality of life increases. The resistance of pathogens to multiple antibiotics is also increasing, adding an additional layer of complexity to the problems of employing safe and effective medical procedures. One approach to reducing the rate of infections associated with implanted and indwelling medical devices is the use of polymers that resist the formation of bacterial biofilms...
December 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29180778/the-development-of-bioresorbable-composite-polymeric-implants-with-high-mechanical-strength
#6
Upma Sharma, Danny Concagh, Lee Core, Yina Kuang, Changcheng You, Quynh Pham, Greg Zugates, Rany Busold, Stephanie Webber, Jonathan Merlo, Robert Langer, George M Whitesides, Maria Palasis
Implants for the treatment of tissue defects should mimic the mechanical properties of the native tissue of interest and should be resorbable as well as biocompatible. In this work, we developed a scaffold from variants of poly(glycolic) acid which were braided and coated with an elastomer of poly(glycolide-co-caprolactone) and crosslinked. The coating of the scaffold with the elastomer led to higher mechanical strength in terms of compression, expansion and elasticity compared to braids without the elastomer coating...
January 2018: Nature Materials
https://www.readbyqxmd.com/read/29158415/long-term-dopamine-neurochemical-monitoring-in-primates
#7
Helen N Schwerdt, Hideki Shimazu, Ken-Ichi Amemori, Satoko Amemori, Patrick L Tierney, Daniel J Gibson, Simon Hong, Tomoko Yoshida, Robert Langer, Michael J Cima, Ann M Graybiel
Many debilitating neuropsychiatric and neurodegenerative disorders are characterized by dopamine neurotransmitter dysregulation. Monitoring subsecond dopamine release accurately and for extended, clinically relevant timescales is a critical unmet need. Especially valuable has been the development of electrochemical fast-scan cyclic voltammetry implementing microsized carbon fiber probe implants to record fast millisecond changes in dopamine concentrations. Nevertheless, these well-established methods have only been applied in primates with acutely (few hours) implanted sensors...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29152410/ultrasound-triggered-local-anaesthesia
#8
Alina Y Rwei, Juan L Paris, Bruce Wang, Weiping Wang, Christopher D Axon, María Vallet-Regí, Robert Langer, Daniel S Kohane
On-demand relief of local pain would allow patients to control the timing, intensity and duration of nerve block in a safe and non-invasive manner. Ultrasound would be a suitable trigger for such a system, as it is in common clinical use and can penetrate deeply into the body. Here, we demonstrate that ultrasound-triggered delivery of an anaesthetic from liposomes allows the timing, intensity and duration of nerve block to be controlled by ultrasound parameters. On insonation, the encapsulated sonosensitizer protoporphyrin IX produces reactive oxygen species that react with the liposomal membrane, leading to the release of the potent local anaesthetic tetrodotoxin...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/29131148/structure-guided-chemical-modification-of-guide-rna-enables-potent-non-viral-in-vivo-genome-editing
#9
Hao Yin, Chun-Qing Song, Sneha Suresh, Qiongqiong Wu, Stephen Walsh, Luke Hyunsik Rhym, Esther Mintzer, Mehmet Fatih Bolukbasi, Lihua Julie Zhu, Kevin Kauffman, Haiwei Mou, Alicia Oberholzer, Junmei Ding, Suet-Yan Kwan, Roman L Bogorad, Timofei Zatsepin, Victor Koteliansky, Scot A Wolfe, Wen Xue, Robert Langer, Daniel G Anderson
Efficient genome editing with Cas9-sgRNA in vivo has required the use of viral delivery systems, which have limitations for clinical applications. Translational efforts to develop other RNA therapeutics have shown that judicious chemical modification of RNAs can improve therapeutic efficacy by reducing susceptibility to nuclease degradation. Guided by the structure of the Cas9-sgRNA complex, we identify regions of sgRNA that can be modified while maintaining or enhancing genome-editing activity, and we develop an optimal set of chemical modifications for in vivo applications...
November 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29120819/towards-a-defined-ecm-and-small-molecule-based-monolayer-culture-system-for-the-expansion-of-mouse-and-human-intestinal-stem-cells
#10
Zhixiang Tong, Keir Martyn, Andy Yang, Xiaolei Yin, Benjamin E Mead, Nitin Joshi, Nicholas E Sherman, Robert S Langer, Jeffrey M Karp
Current ISC culture systems face significant challenges such as animal-derived or undefined matrix compositions, batch-to-batch variability (e.g. Matrigel-based organoid culture), and complexity of assaying cell aggregates such as organoids which renders the research and clinical translation of ISCs challenging. Here, through screening for suitable ECM components, we report a defined, collagen based monolayer culture system that supports the growth of mouse and human intestinal epithelial cells (IECs) enriched for an Lgr5(+) population comparable or higher to the levels found in a standard Matrigel-based organoid culture...
October 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/29026204/engineering-and-physical-sciences-in-oncology-challenges-and-opportunities
#11
REVIEW
Michael J Mitchell, Rakesh K Jain, Robert Langer
The principles of engineering and physics have been applied to oncology for nearly 50 years. Engineers and physical scientists have made contributions to all aspects of cancer biology, from quantitative understanding of tumour growth and progression to improved detection and treatment of cancer. Many early efforts focused on experimental and computational modelling of drug distribution, cell cycle kinetics and tumour growth dynamics. In the past decade, we have witnessed exponential growth at the interface of engineering, physics and oncology that has been fuelled by advances in fields including materials science, microfabrication, nanomedicine, microfluidics, imaging, and catalysed by new programmes at the National Institutes of Health (NIH), including the National Institute of Biomedical Imaging and Bioengineering (NIBIB), Physical Sciences in Oncology, and the National Cancer Institute (NCI) Alliance for Nanotechnology...
November 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28993678/erratum-characterization-of-mechanically-matched-hydrogel-coatings-to-improve-the-biocompatibility-of-neural-implants
#12
Kevin C Spencer, Jay C Sy, Khalil B Ramadi, Ann M Graybiel, Robert Langer, Michael J Cima
A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28991392/ambireactive-r%C3%A2-p-%C3%A2-bh%C3%A2-groups-facilitating-temperature-switchable-bond-activation-by-an-iron-complex
#13
Lisa Vondung, Lars Erik Sattler, Robert Langer
An iron pincer complex containing a hemi-labile (R₃P)₂BH₂-group exhibits temperature-switchable reactivity patterns: a reversible B-H-activation concomitant with a P-B-bond cleavage is observed at room temperature. Below 4 °C intra- and inter-molecular C-H-activation pathways are becoming faster and dominating. Mechanistic investigations reveal that the lability of the (R₃P)₂BH₂-group in combination with the exothermic formation of σ-bonded complexes are responsible for the switchable bond activation...
October 9, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28974673/mechanistic-understanding-of-in-vivo-protein-corona-formation-on-polymeric-nanoparticles-and-impact-on-pharmacokinetics
#14
Nicolas Bertrand, Philippe Grenier, Morteza Mahmoudi, Eliana M Lima, Eric A Appel, Flavio Dormont, Jong-Min Lim, Rohit Karnik, Robert Langer, Omid C Farokhzad
In vitro incubation of nanomaterials with plasma offer insights on biological interactions, but cannot fully explain the in vivo fate of nanomaterials. Here, we use a library of polymer nanoparticles to show how physicochemical characteristics influence blood circulation and early distribution. For particles with different diameters, surface hydrophilicity appears to mediate early clearance. Densities above a critical value of approximately 20 poly(ethylene glycol) chains (MW 5 kDa) per 100 nm2 prolong circulation times, irrespective of size...
October 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28963481/synthetic-microparticles-conjugated-with-vegf165-improve-the-survival-of-endothelial-progenitor-cells-via-microrna-17-inhibition
#15
Sezin Aday, Janet Zoldan, Marie Besnier, Laura Carreto, Jaimy Saif, Rui Fernandes, Tiago Santos, Liliana Bernardino, Robert Langer, Costanza Emanueli, Lino Ferreira
Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy. Here, we report a pro-survival approach based on VEGF-immobilized microparticles (VEGF-MPs)...
September 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28945422/living-biomaterials
#16
Mark W Tibbitt, Robert Langer
Convergent advances in the fields of synthetic chemistry, soft matter, molecular self-assembly, and the -omics era point to a new generation of synthetic biomaterials that are indistinguishable in form and function from biological matter. Such living biomaterials comprise a "Holy Grail" of the chemical sciences that will transform both modern medicine and materials design.
March 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28937662/glucose-responsive-insulin-by-molecular-and-physical-design
#17
Naveed A Bakh, Abel B Cortinas, Michael A Weiss, Robert S Langer, Daniel G Anderson, Zhen Gu, Sanjoy Dutta, Michael S Strano
The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker...
September 22, 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28932622/high-throughput-nuclear-delivery-and-rapid-expression-of-dna-via-mechanical-and-electrical-cell-membrane-disruption
#18
Xiaoyun Ding, Martin Stewart, Armon Sharei, James C Weaver, Robert S Langer, Klavs F Jensen
Nuclear transfection of DNA into mammalian cells is challenging yet critical for many biological and medical studies. Here, by combining cell squeezing and electric-field-driven transport in a device that integrates microfluidic channels with constrictions and microelectrodes, we demonstrate nuclear delivery of plasmid DNA within 1 hour after treatment, the most rapid DNA expression in a high-throughput setting (up to millions of cells per minute per device). Passing cells at high speed through microfluidic constrictions smaller than the cell diameter mechanically disrupts the cell membrane, allowing a subsequent electric field to further disrupt the nuclear envelope and drive DNA molecules into the cytoplasm and nucleus...
2017: Nature Biomedical Engineering
https://www.readbyqxmd.com/read/28912242/fabrication-of-fillable-microparticles-and-other-complex-3d-microstructures
#19
Kevin J McHugh, Thanh D Nguyen, Allison R Linehan, David Yang, Adam M Behrens, Sviatlana Rose, Zachary L Tochka, Stephany Y Tzeng, James J Norman, Aaron C Anselmo, Xian Xu, Stephanie Tomasic, Matthew A Taylor, Jennifer Lu, Rohiverth Guarecuco, Robert Langer, Ana Jaklenec
Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile drug-delivery microparticles, pH sensors, and 3D microfluidic devices that we could not produce using traditional 3D printing...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28903368/expression-analysis-of-lc3b-and-p62-indicates-intact-activated-autophagy-is-associated-with-an-unfavorable-prognosis-in-colon-cancer
#20
Monique Niklaus, Olivia Adams, Sabina Berezowska, Inti Zlobec, Franziska Graber, Julia Slotta-Huspenina, Ulrich Nitsche, Robert Rosenberg, Mario P Tschan, Rupert Langer
Autophagy is a lysosomal degradation and recycling process implicated in cancer progression and therapy resistance. We assessed the impact of basal autophagy in colon cancer (CC) in vitro and ex vivo. Functional autophagy was demonstrated in CC cell lines (LoVo; HT-29) showing a dose-dependent increase of the autophagy markers LC3B, p62 and autophagic vesciles upon increasing concentrations of the autophagy inhibitor chloroquine, which was demonstrated by immunoblotting, immunofluorescence and electron microscopy...
August 15, 2017: Oncotarget
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