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| Open AccessA genetically encoded sensor for visualizing leukotriene B4 gradients in vivo
Leukotriene B4 (LTB4) is a potent lipid chemoattractant driving leukocyte migration and neutrophil swarming, but methods for its real-time detection are lacking. Here, the authors develop GEM-LTB4, a genetically encoded fluorescent biosensor, and use it to visualize leukocyte-derived LTB4 gradients.
- Szimonetta Xénia Tamás
- , Benoit Thomas Roux
- & Balázs Enyedi
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Article
| Open AccessRapid prototyping of high-resolution large format microfluidic device through maskless image guided in-situ photopolymerization
The utility of microfluidic devices has been limited by several drawbacks including low resolution, inferior feature fidelity, poor repeatability. Here the authors address these challenges by developing a strategic approach of image guided in-situ maskless lithography to fabricate a variety of microfluidic devices and resolve critical proximity effect and size limitations in rapid prototyping.
- Ratul Paul
- , Yuwen Zhao
- & Yaling Liu
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Article
| Open AccessRapid genetic screening with high quality factor metasurfaces
The authors present a high quality factor metasurface that enables sensitive and highly-parallelized detection of biomolecules. Amplification-free detection of gene fragments down to femtomolar levels is demonstrated within 5 minutes, for rapid nucleic acid analysis.
- Jack Hu
- , Fareeha Safir
- & Jennifer A. Dionne
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Article
| Open AccessPreventing cation intermixing enables 50% quantum yield in sub-15 nm short-wave infrared-emitting rare-earth based core-shell nanocrystals
Controlling cation intermixing in rare-earth based core-shell nanomaterials is a key strategy to improve the emission properties. Here the authors address this challenge by controlling the growth of heterogeneous structures, obtaining 50% short-wavelength infrared quantum yield in sub-15 nm Ce-doped α-NaYF4:Yb:Er@CaF2 nanocrystals.
- Fernando Arteaga Cardona
- , Noopur Jain
- & Damien Hudry
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Article
| Open AccessIn situ assembly of bioresorbable organic bioelectronics in the brain
Temporary bioelectronics can complement classical therapies in non-chronic treatments. Here, the authors describe the minimally invasive implantation of bioresorbable electrodes in the brain that form in situ from water-dispersed nanoparticles and show no tissue damage after bioresorption.
- Martin Hjort
- , Abdelrazek H. Mousa
- & Roger Olsson
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Article
| Open AccessPrecise in-field molecular diagnostics of crop diseases by smartphone-based mutation-resolved pathogenic RNA analysis
On-site crop disease diagnostics is critical for precise application of pesticides. Here, the authors report an in-field molecular diagnostic tool for wheat pathogens using a nucleic acid amplification-free, gene mutation-resolved and smartphone-integrated genetic assay.
- Ting Zhang
- , Qingdong Zeng
- & Ruijie Deng
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Article
| Open AccessMultiplexed RNA profiling by regenerative catalysis enables blood-based subtyping of brain tumors
Current methods to subtype brain tumors rely on invasive biopsies. Here, the authors develop a digital platform to regeneratively convert and catalytically enhance signals from rare circulating RNAs for blood-based characterization of brain tumors.
- Yan Zhang
- , Chi Yan Wong
- & Huilin Shao
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Article
| Open AccessmRNA lipid nanoparticle-mediated pyroptosis sensitizes immunologically cold tumors to checkpoint immunotherapy
mRNA nanomedicine-based gene therapy may offer opportunities for cancer treatment. Here the authors show that mRNA lipid nanoparticles encoding the N-terminal domain of gasdermin B trigger pyroptosis and promote anti-tumor immune responses in preclinical cancer models.
- Fengqiao Li
- , Xue-Qing Zhang
- & Xiaoyang Xu
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Article
| Open AccessExtending the dynamic range of biomarker quantification through molecular equalization
The human plasma proteome spans over 10 orders of magnitude, but current quantification methods cover only 3-4 orders. Here, authors propose a tuning approach for proximity-based assays, enabling simultaneous quantification of four analytes across a wide concentration range (low fM to mid-nM).
- Sharon S. Newman
- , Brandon D. Wilson
- & H. Tom Soh
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Article
| Open AccessReal-time environmental surveillance of SARS-CoV-2 aerosols
Rapid detection of respiratory pathogens circulating in indoor environments could facilitate improved infection prevention responses. In this proof-of-concept study, the authors develop a pathogen air quality monitor for real-time direct detection of SARS-CoV-2 aerosols and demonstrate its application in rooms of people with SARS-CoV-2 infections.
- Joseph V. Puthussery
- , Dishit P. Ghumra
- & Rajan K. Chakrabarty
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Article
| Open AccessMultiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function
ApoE is known to be important for lipid nanoparticle function. Here, the authors shows that efficacious coronal ApoE originates from high-density lipoprotein (HDL) particles and, enhances hepatic delivery, making HDL a superior biomarker for lipid nanoparticle potency.
- Kai Liu
- , Ralf Nilsson
- & Alan Sabirsh
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Article
| Open AccessUltrasound-responsive low-dose doxorubicin liposomes trigger mitochondrial DNA release and activate cGAS-STING-mediated antitumour immunity
Chemotherapy-induced cytosolic DNA has been shown to activate the cGAS-STING pathway. Here, the authors demonstrate that the efficacy of low-dose doxorubicin to elicit a STING-mediated anti-tumour immune response can be enhanced by liposomal-loading with indocyanine green, resulting in ultrasound-activatable enhanced nuclear doxorubicin localisation and release of mitochondrial DNA.
- Chaoyu Wang
- , Ruoshi Zhang
- & Rui Kuai
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Article
| Open AccessStructure and dynamics of an archetypal DNA nanoarchitecture revealed via cryo-EM and molecular dynamics simulations
DNA can be folded into rationally designed, unique, and functional materials. Here the authors analyse an archetypal DNA nanoarchitecture with single particle cryo-electron microscopy and molecular dynamics simulations.
- Katya Ahmad
- , Abid Javed
- & Stefan Howorka
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Article
| Open AccessRatiometric measurement of MAM Ca2+ dynamics using a modified CalfluxVTN
MAM Ca2+ dynamics play an important role in diverse biological processes, but directly and specifically measuring Ca2+ concentrations in this region is technically challenging. Here the authors report a MAM-specific BRET-based Ca2+ indicator called MAM-Calflux, which works as both a Ca2+ indicator and a structural marker due to its ratiometric nature.
- Eunbyul Cho
- , Youngsik Woo
- & Sang Ki Park
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Article
| Open AccessVitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model
The possibility of banking cryopreserved organs could make transplantation medicine much more accessible. Here, the authors show that vitrification and nanowarming—cooling organs to an ice-free state followed by rapid rewarming using nanoparticles and magnetic fields—enables organ cryopreservation, long-term banking, and recovery of full function in a rat kidney transplant model.
- Zonghu Han
- , Joseph Sushil Rao
- & Erik B. Finger
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Article
| Open AccessA mutation in switch I alters the load-dependent kinetics of myosin Va
Myosin transduces chemical energy into mechanical work, but the mechanism remains unclear. In this work, the authors show that force-generation precedes product release and that a mutation in the active site alters the load dependence of product release.
- Christopher Marang
- , Brent Scott
- & Edward P. Debold
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Article
| Open AccessIntracellular RNA and DNA tracking by uridine-rich internal loop tagging with fluorogenic bPNA
Commonly used protein-based tools to monitor intracellular RNA and DNA can impact steric accessibility and native nucleic acid biology. Here, the authors show that fluorogenic uridine-rich internal loop tagging bPNA probes can be used to label nucleic acids in fixed and live cells.
- Yufeng Liang
- , Sydney Willey
- & Dennis Bong
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Article
| Open AccessA smart pathogen detector engineered from intracellular hydrogelation of DNA-decorated macrophages
Macrophages have the inherent capacity to recognise pathogenic microorganisms, highlighting their potential to be used in biosensing applications. Herein, the authors report a method to transform normally fragile macrophages into robust gelated cell particles for efficient bacterial capture and detection.
- Yueyue Gui
- , Yujing Zeng
- & Chao Li
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Article
| Open AccessMoS2 nanopore identifies single amino acids with sub-1 Dalton resolution
Protein sequencing is one of the key aims of the nanopore field. Working toward this goal, here the authors report the direct identification of single amino acids in MoS2 nanopores with sub-1 Dalton resolution, as well as the discrimination of the amino acid isomers and amino acid phosphorylation.
- Fushi Wang
- , Chunxiao Zhao
- & Jiandong Feng
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Article
| Open AccessA local water molecular-heating strategy for near-infrared long-lifetime imaging-guided photothermal therapy of glioblastoma
Neodymium (Nd)-doped nanoparticles have been described for imaging-guided photothermal therapy. Here the authors design a Nd-Yb co-doped nanomaterial as nearinfrared long-lifetime imaging-guided waterheating probe, showing photothermal ablation in a glioblastoma pre-clinical mode
- Dongkyu Kang
- , Hyung Shik Kim
- & Joonseok Lee
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Article
| Open AccessHigh-throughput single nucleus total RNA sequencing of formalin-fixed paraffin-embedded tissues by snRandom-seq
Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank, but single nucleus RNAseq using such tissues is challenging. Here the authors develop a droplet-based method called snRandom-seq for high-throughput and sensitive single nucleus RNA-seq of FFPE samples.
- Ziye Xu
- , Tianyu Zhang
- & Yongcheng Wang
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Article
| Open AccessIn situ continuous Dopa supply by responsive artificial enzyme for the treatment of Parkinson’s disease
Oral dihydroxyphenylalanine (Dopa) administration to replenish neuronal dopamine is a treatment for Parkinson’s disease but induces fluctuations in plasma Dopa levels. Here the authors report a nucleic acid-based responsive artificial enzyme (FNA-Fe3O4) for in situ continuous Dopa production.
- Xiao Fang
- , Meng Yuan
- & Huanghao Yang
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Article
| Open AccessHigh-resolution discrimination of homologous and isomeric proteinogenic amino acids in nanopore sensors with ultrashort single-walled carbon nanotubes
Ultrashort single-walled carbon nanotubes inserted in lipid bilayers can be used as nanopore sensors. Here, the authors demonstrate the high-resolution discrimination of homologous and isomeric proteinogenic amino acids with such carbon-based nanopores.
- Weichao Peng
- , Shuaihu Yan
- & Yuliang Zhao
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Article
| Open AccessNanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation
TRPV1 has been associated with proliferation and survival of tumors, and can be activated by heat and other stimuli. Here, the authors block TRPV1 using photothermal nanoparticles encapsulating a TRPV1 antagonist in different cancer types, which can enhance thermo-immunotherapy in pancreatic cancer models.
- Ting Li
- , Shuhui Jiang
- & Huabing Chen
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Article
| Open AccessRAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes
Mechanical forces drive critical cellular processes, but methods to study such cellular forces are typically low-throughput. Here the authors present a method using “Rupture And Deliver” Tension Gauge Tethers, where flow cytometry or sequencing can be used to record the mechanical history of thousands of individual cells.
- Matthew R. Pawlak
- , Adam T. Smiley
- & Wendy R. Gordon
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Article
| Open AccessIn vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter
Bioluminescent imaging of bacteria in vivo generally requires the use of engineered bacteria. Here the authors take advantage of bacteria specific ATP-binding cassette sugar transporters to enable selective delivery of bioluminescent nanoprobes into bacteria for visualisation, including in deep tissues.
- Qian Zhang
- , Bin Song
- & Yao He
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Article
| Open AccessTrumpet is an operating system for simple and robust cell-free biocomputing
Biological computation is becoming a viable and fast-growing alternative to traditional electronic computing. Here the authors present Trumpet, which uses DNA and enzymes to build logic gate circuits with amplified fluorescent readout.
- Judee A. Sharon
- , Chelsea Dasrath
- & Katarzyna P. Adamala
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Article
| Open AccessTemperature sensitive liposome based cancer nanomedicine enables tumour lymph node immune microenvironment remodelling
The tumour lymph node microenvironment is an important contributor to the immune suppressiveness of tumours. Here authors target the tumours and the lymph node simultaneously via a pH and photothermal therapy targeted nanoparticle, and show mobilisation of anti-tumour cytotoxic T cells and NK cells and synergistic therapeutic effect with immune checkpoint blockade.
- Shunli Fu
- , Lili Chang
- & Na Zhang
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Article
| Open AccessIn mitosis integrins reduce adhesion to extracellular matrix and strengthen adhesion to adjacent cells
Adopting a round cell morphology before mitosis is crucial. Here, the authors show that in mitosis integrins binding to ligands do not engage the actomyosin cortex, which curbs cell-extracellular matrix adhesion, though β1 integrins are rewired to synergize with cadherins in mitotic cell-cell adhesion.
- Maximilian Huber
- , Javier Casares-Arias
- & Nico Strohmeyer
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Article
| Open AccessSingle-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore
Efficient screening of protein-drug interactions (PDIs) has been impeded by the limitations of current biophysical approaches. Here, the authors present a funneled YaxAB nanopore sensor which allows label-free, single-molecule detection of proteins and PDIs.
- Ki-Baek Jeong
- , Minju Ryu
- & Seung-Wook Chi
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Article
| Open AccessSelf assembling nanoparticle enzyme clusters provide access to substrate channeling in multienzymatic cascades
Channeling between enzymes is a uniquely nanoscale phenomenon that can improve multienzymatic reaction rates. Here, the authors demonstrate that multistep enzyme cascades can self-assemble with nanoparticles into nanoclusters that access channeling and improve the underlying catalytic flux by several fold.
- Joyce C. Breger
- , James N. Vranish
- & Igor L. Medintz
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Article
| Open AccessIdentification of tagged glycans with a protein nanopore
The structural complexity of glycans seriously challenges the currently available analytical methods. Here, the authors report the identification of glycan isomers, glycans with varying chain lengths, and distinct branched glycans, via a glycan derivatization strategy and nanopore sensing.
- Minmin Li
- , Yuting Xiong
- & Guangyan Qing
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Article
| Open AccessSmall molecule-nanobody conjugate induced proximity controls intracellular processes and modulates endogenous unligandable targets
Induced proximity can be used to control diverse cellular processes. Here, the authors develop nanobody-based proximity inducers called SNACIPs, which can be used to regulate either tagged or endogenous proteins, and demonstrate their use in blocking microtubule nucleation for tumour growth inhibition in vivo.
- Xiaofeng Sun
- , Chengjian Zhou
- & Xi Chen
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Article
| Open AccessSingle test-based diagnosis of multiple cancer types using Exosome-SERS-AI for early stage cancers
Early detection of multiple cancers through a single method could be clinically important. Here the authors report the diagnostic performance for early detection for multiple cancers using surface-enhanced Raman spectroscopy (SERS) profiles of exosomes from a single blood test and artificial intelligence in a retrospective study design.
- Hyunku Shin
- , Byeong Hyeon Choi
- & Yeonho Choi
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| Open AccessA generalizable nanopore sensor for highly specific protein detection at single-molecule precision
Sensitive and accurate approaches for protein detection have many potential applications. Here the authors show how engineered protein nanopore sensors, consisting of a monobody fused to a single-polypeptide nanopore, can be used for highly specific detection of proteins in complex biofluids.
- Mohammad Ahmad
- , Jeung-Hoi Ha
- & Liviu Movileanu
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Article
| Open AccessModeling of three-dimensional innervated epidermal like-layer in a microfluidic chip-based coculture system
Skin-nerve crosstalk is a major element of skin physiological pathology. Here the authors report a 3D innervated epidermal keratinocyte layer as a sensory neuron-epidermal keratinocyte coculture model on a microfluidic chip using the slope-based air-liquid interfacing culture and spatial compartmentalization.
- Jinchul Ahn
- , Kyungeun Ohk
- & Sang-Hoon Lee
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Review Article
| Open AccessSmartphone-based platforms implementing microfluidic detection with image-based artificial intelligence
Smartphone-based mobile health platforms have drawn increasing attention from researchers developing point-of-care testing devices. Here the authors summarize recent progress and future directions of approaches combining microfluidics and artificial intelligence.
- Bangfeng Wang
- , Yiwei Li
- & Bi-Feng Liu
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Article
| Open AccessCreating complex protocells and prototissues using simple DNA building blocks
Building synthetic protocells and prototissues hinges on the formation of biomimetic skeletal frameworks. Here, the authors harness simplicity to create complexity by assembling DNA subunits into structural frameworks which support membrane-based protocells and prototissues.
- Nishkantha Arulkumaran
- , Mervyn Singer
- & Jonathan R. Burns
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Article
| Open AccessLantern-shaped flexible RNA origami for Smad4 mRNA delivery and growth suppression of colorectal cancer
mRNA delivery has shown great potential in the treatment of various diseases. Here, the authors develop a lantern-shaped flexible origami for nanolization of single mRNA molecules and demonstrate efficient delivery of Smad4 mRNA, achieving suppression of colorectal cancer tumour growth.
- Muren Hu
- , Chang Feng
- & Xiaoli Zhu
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Article
| Open AccessBright Tm3+-based downshifting luminescence nanoprobe operating around 1800 nm for NIR-IIb and c bioimaging
Fluorescence imaging in the near-infrared region yields high-quality images that overcome the current depth limitations. Here, the authors report a Tm3 + -based nanoprobe for NIR-IIb/c imaging, providing references to future bioimaging beyond 1700 nm.
- Yulei Chang
- , Haoren Chen
- & Xianggui Kong
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Article
| Open AccessSnake venom-defined fibrin architecture dictates fibroblast survival and differentiation
A new snake venom-controlled defined fibrin system with stable, reproducible, and independently tuned biophysical properties is established. Employing the system, the authors find fibrin architecture can precisely control fibroblast differentiation.
- Zhao Wang
- , Jan Lauko
- & Alan E. Rowan
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Article
| Open AccessAntigen footprint governs activation of the B cell receptor
The antigen-B-cell-receptor interaction is the driving force of terminal B cell development that spans from B cell activation to antibody secreting plasma cells. Here authors determine, using DNA-PAINT super-resolution microscopy, how antigen affinity and valency define antigen binding to BCR in an in vitro system allowing precision control of these parameters.
- Alexey Ferapontov
- , Marjan Omer
- & Søren Egedal Degn
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Article
| Open AccessFluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats
Delivery of anti-inflammatory microRNA (miRNA) could be beneficial for inflammatory diseases such as rheumatoid arthritis (RA). Here the authors show that a fluorinated polyamidoamine dendrimer nanoparticle delivers miR-23b to affected RA joints and reduces inflammation, joint damage and synovial cell influx.
- Haobo Han
- , Jiakai Xing
- & Quanshun Li
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Article
| Open AccessRemodeling articular immune homeostasis with an efferocytosis-informed nanoimitator mitigates rheumatoid arthritis in mice
Proinflammatory macrophages are involved in rheumatoid arthritis (RA). Here the authors use an efferocytosis-mimetic self-deliverable nanoimitator to mitigate RA by targeted reprogramming of synovial inflammatory macrophages, reducing proinflammatory cytokines and reinstating articular immune homeostasis.
- Shengchang Zhang
- , Ying Liu
- & Xinyi Jiang
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Article
| Open AccessDirect digital sensing of protein biomarkers in solution
There are limitations with current protein sensing methods. Here the authors report DigitISA, a digital immunosensor assay based on microchip electrophoretic separation and single-molecule detection that enables quantitation of protein biomarkers in a single, solution-phase step.
- Georg Krainer
- , Kadi L. Saar
- & Tuomas P. J. Knowles
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Article
| Open AccessA supramolecular cucurbit[8]uril-based rotaxane chemosensor for the optical tryptophan detection in human serum and urine
Sensing small biomolecules in biofluids using host-guest chemosensors remains challenging, in part due to the impact of interfering components. Here, the authors develop a dual-macrocyclic rotaxane for tryptophan detection which can function in biofluids such as human serum and urine.
- Joana Krämer
- , Laura M. Grimm
- & Frank Biedermann
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Article
| Open Access3D RNA-scaffolded wireframe origami
Hybrid nucleic acid origami has potential for biomedical delivery of mRNA and fabrication of artificial ribozymes. Here, the authors use chemical footprinting and cryo-electron microscopy to reveal insights into nucleic acid origami used to fold messenger and ribosomal RNA into 3D polyhedral structures.
- Molly F. Parsons
- , Matthew F. Allan
- & Mark Bathe
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Article
| Open AccessIn-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
Cryosurgery can represent a therapeutic option for breast cancer treatment. Here the authors report a strategy combining cryosurgery with cold-responsive nanoparticles loaded with the chemotherapeutic drug irinotecan and PD-L1-targeting siRNA, inducing anti-tumor immune responses in preclinical breast cancer models.
- Wenquan Ou
- , Samantha Stewart
- & Xiaoming He
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Article
| Open AccessDifferential sensing with arrays of de novo designed peptide assemblies
Differential sensing aims to mimic senses such as taste and smell through the use of synthetic receptors. Here, the authors show that arrays of de novo designed peptide assemblies can be used as sensor components to distinguish various analytes and complex mixtures.
- William M. Dawson
- , Kathryn L. Shelley
- & Derek N. Woolfson