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| Open AccessRectifying disorder of extracellular matrix to suppress urethral stricture by protein nanofilm-controlled drug delivery from urinary catheter
Various anti-fibrotic drugs have been applied to urethral stricture by irrigation or submucosal injection, but their clinical feasibility and effectiveness are limited. Here, the authors design a protein-based nanofilm-controlled drug delivery system with anti-biofilm properties that can be assembled on a catheter.
- Juanhua Tian
- , Delai Fu
- & Peng Yang
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Article
| Open AccessEfficient selective removal of uremic toxin precursor by olefin-linked covalent organic frameworks for nephropathy treatment
Indoxyl sulfate is a key risk factor in the progression of chronic kidney disease, but cannot be removed from the blood by hemodialysis. Here, the authors report the use of a covalent organic framework for the removal of indoxyl sulfate precursor from the intestine.
- Jinxia Wei
- , Rui Li
- & Yao Chen
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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 AccessNon-enzymatic oligonucleotide ligation in coacervate protocells sustains compartment-content coupling
Achieving a form of coupling between molecular content, chemical reactions, and chassis in synthetic compartments represents a key step to the assembly of evolvable protocells but remains challenging. Here, the authors design coacervate droplets that promote non-enzymatic oligonucleotide polymerization and that restructure as a result of the reaction dynamics.
- Tommaso P. Fraccia
- & Nicolas Martin
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Article
| Open AccessRestoration of lysosomal acidification rescues autophagy and metabolic dysfunction in non-alcoholic fatty liver disease
In NAFLD, high levels of fatty acids in the liver impair lysosomal acidification. Here, the authors report the synthesis of novel biodegradable acid-activated acidifying nanoparticles that re-acidify lysosomes, restore autophagy, and reverse fasting hyperglycemia and hepatic steatosis in fat mice.
- Jialiu Zeng
- , Rebeca Acin-Perez
- & Mark W. Grinstaff
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Article
| Open AccessFueling sentinel node via reshaping cytotoxic T lymphocytes with a flex-patch for post-operative immuno-adjuvant therapy
Sentinel lymph nodes (SLNs) represent the sites where micro-metastasis can first develop, however they are also important to mount effective anti-tumor immune responses. Here the authors describe the design of a flex-patch loaded with anti-PD-1 antibodies and immuno-adjuvant nanosheets, layered double hydroxide, to fuel anti-tumor immune response in the SLN for postsurgical breast cancer adjuvant therapy.
- Bei Li
- , Guohao Wang
- & Yunlu Dai
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Article
| Open AccessHydrogel dressing integrating FAK inhibition and ROS scavenging for mechano-chemical treatment of atopic dermatitis
Mechanical scratching and oxidative stress can aggravate atopic dermatitis symptoms, while treatment targeting scratching is often overlooked. Here, the authors find that enhanced phosphorylation of focal adhesion kinase is associated with scratch-exacerbated AD, then develop a hydrogel dressing that integrates oxidative stress modulation with FAK inhibition to synergistically treat AD.
- Yuanbo Jia
- , Jiahui Hu
- & Feng Xu
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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 AccessCargo-free particles divert neutrophil-platelet aggregates to reduce thromboinflammation
Platelet-neutrophil aggregates are a hallmark of thromboinflamation. Here, the authors use cargo-free particles to block platelet-neutrophil aggregates’ vascular wall adhesion, which could become an effective thromboinflammation therapy, regardless of disease cause.
- Alison L. Banka
- , M. Valentina Guevara
- & Omolola Eniola-Adefeso
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Article
| Open AccessAn aptamer-based depot system for sustained release of small molecule therapeutics
Controlled delivery of small molecule therapeutics is challenging. Here the authors report a simple and effective aptamer-based depot system where the formation of aptamer/drug complexes leads to sustained release, and using this approach demonstrate improved in vivo delivery of channel blockers.
- Dali Wang
- , Yang Li
- & Christopher B. Weldon
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Article
| Open AccessExploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch
Autologous skin flap transplantation is a common method to repair complex soft tissue defects. Here the authors develop a hydrogel patch that releases carbon monoxide and nitric oxide gases on demand, to afford a timely blood supply for skin flap transplantation during surgery, just improving the incidence of distal necrosis of the flap and reducing long-term functional loss.
- Xiaoduo Tang
- , Jingyan Ren
- & Bai Yang
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Article
| Open AccessBioinspired artificial spider silk photocatalyst for the high-efficiency capture and inactivation of bacteria aerosols
Bioaerosol can cause the spread of disease, but current removal systems are easily blocked and often cannot deactivate the bioaerosol. Here, the authors report a method for bioaerosol removal and deactivation using a bioinspired photocatalyst capable of capturing airborne bacteria.
- Linghui Peng
- , Haiyu Wang
- & Taicheng An
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Article
| Open AccessA massively parallel screening platform for converting aptamers into molecular switches
Efforts to convert aptamers into molecular switches using rational design are often unsuccessful. Here the authors describe a massively parallel screening-based strategy whereby millions of potential aptamer switches are synthesised, sequenced and screened directly on a flow-cell.
- Alex M. Yoshikawa
- , Alexandra E. Rangel
- & H. Tom Soh
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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 AccessGrowth dynamics and amorphous-to-crystalline phase transformation in natural nacre
Biominerals contain trace elements that can give important environmental information, but the mechanism by which these are incorporated into the structure is not well understood. Here, the authors explore the crystallization pathways involved in the formation of nacre, and how these affect the incorporation of trace elements.
- L. M. Otter
- , K. Eder
- & D. E. Jacob
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Article
| Open AccessHighly conductive tissue-like hydrogel interface through template-directed assembly
Conductive hydrogels have potential as tissue-interfacing electrodes, but it is challenging to achieve both robust mechanical properties and good electrical properties. Here, the authors report a synthetic method for developing highly conductive and mechanically tough hydrogels, with a tissue-like modulus, for electrocardiogram signal recording.
- Jooyeun Chong
- , Changhoon Sung
- & Jiheong Kang
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Article
| Open AccessExtracellular vesicles engineering by silicates-activated endothelial progenitor cells for myocardial infarction treatment in male mice
Extracellular vesicle therapy has shown great potential for the treatment of myocardial infarction. Here, the authors show a silicate biomaterials-based approach to engineer extracellular vesicles from endothelial progenitor cells with high yield and bioactivity for treating myocardial infarction.
- Bin Yu
- , Hekai Li
- & Caiwen Ou
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Article
| Open AccessLeaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities
Recapitulating the native architecture of myocardium is crucial to engineering functional cardiac tissues. Here, the authors develop a leaf-venation-directed strategy for macroscale cardiac constructs with tissue-like structural, mechanical, and electrophysiological properties.
- Mao Mao
- , Xiaoli Qu
- & Dichen Li
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Article
| Open AccessCollagen breaks at weak sacrificial bonds taming its mechanoradicals
Collagen is an important structural protein in connective tissue, but the effect of location and type of micro-ruptures in the structure on the overall tissue is not well understood. Here, the authors use scale-bridging simulations to determine the breakage points in collagen, and how the failure mode helps to prevent material ageing
- Benedikt Rennekamp
- , Christoph Karfusehr
- & Frauke Gräter
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Article
| Open AccessA neutrophil mimicking metal-porphyrin-based nanodevice loaded with porcine pancreatic elastase for cancer therapy
Porcine neutrophil elastase (PPE) has been demonstrated to have a histone H1 isoform dependent anti-tumour effect. Here, the authors develop a biomimetic nanoplatform combining PPE and elevated histone H1 release induced by porphyrin nuclear localisation signal peptide and demonstrate its efficacy in preclinical cancer models.
- Tingting Cui
- , Yu Zhang
- & Xiaogang Qu
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Article
| Open AccessEngineering tumor-specific gene nanomedicine to recruit and activate T cells for enhanced immunotherapy
Intratumoral abundance of chemokines, such as CXCL9, is an important driver of T cell infiltration in tumors. Here the authors describe the design of a tumor-specific expression strategy to drive secretion of CXCL9 and an anti-PD-L1 scFv (αPD-L1) in the tumor microenvironment, promoting T cell recruitment and anti-tumor immune response in preclinical cancer models.
- Yue Wang
- , Shi-Kun Zhou
- & Jun Wang
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Article
| Open AccessLocalized nuclear reaction breaks boron drug capsules loaded with immune adjuvants for cancer immunotherapy
Boron neutron capture therapy (BNCT) is a type of radiotherapy that induces cell damage through a localized nuclear reaction. Here the authors describe the design of a carborane-based covalent organic framework as a boron capsule loaded with immune adjuvants for concurrent BNCT and immunotherapy, promoting anti-tumour immune responses in preclinical cancer models.
- Yaxin Shi
- , Zhibin Guo
- & Zhibo Liu
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Article
| Open AccessIn situ orderly self-assembly strategy affording NIR-II-J-aggregates for in vivo imaging and surgical navigation
J-aggregation, is an effective strategy to extend the wavelength of organic NIR-II fluorescence dyes but weak intermolecular interactions often lead to decomposition of the aggregates in biological environment. Here, the authors demonstrate a series of activatable quinazoline derivatives which can self-assemble in vivo into highly stable NIR-IIJ-aggregates.
- Zhe Li
- , Ping-Zhao Liang
- & Xiao-Bing Zhang
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Article
| Open AccessTransmembrane signaling by a synthetic receptor in artificial cells
Transmembrane signaling is the core adaptation in nature that allows cells to communicate. Here, the authors engineer signaling through the lipid bilayer using chemical, synthetic receptors for their use in the design of artificial cells.
- Ane Bretschneider Søgaard
- , Andreas Bøtker Pedersen
- & Alexander N. Zelikin
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Article
| Open AccessWavelength engineerable porous organic polymer photosensitizers with protonation triggered ROS generation
Engineering excitation wavelength of photosensitizers allows to enhanced reactive oxygen species but controlling the wavelength corresponding to operating conditions remains challenging. Here, the authors implement a wavelength-engineerable imidazolium-based porous organic polymer and demonstrate tuning of the optimal wavelength for maximum performance by modifying the linker system.
- Jinwoo Shin
- , Dong Won Kang
- & Chang Seop Hong
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Article
| Open AccessRobust flexural performance and fracture behavior of TiO2 decorated densified bamboo as sustainable structural materials
Fast-growing bamboo still need advanced processing before being fabricated into sustainable structural materials. Here, the authors develop high-performance TiO2 reinforced densified bamboo via in situ hydrothermal synthesis and reveal the flexural failure mechanism of the composite.
- Ziyu Ba
- , Hongyun Luo
- & Robert O. Ritchie
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Article
| Open AccessControlling extrudate volume fraction through poroelastic extrusion of entangled looped fibers
When a suspension of particles passes through a constriction the particle volume fraction either decreases or remains the same. Pan et al. report that an entangled fiber suspension increases its volume fraction greater than a factor of 10 after passing through a constriction.
- Zehao Pan
- , Janine K. Nunes
- & Howard A. Stone
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Article
| Open AccessTurning dead leaves into an active multifunctional material as evaporator, photocatalyst, and bioplastic
Large numbers of leaves fall off trees each autumn. Here, the authors turn dead leaves into an active material which acts as bioplastic and shows high performance in solar water evaporation, photocatalytic H2 production and antibiotic degradation.
- Siyuan Fang
- , Xingyi Lyu
- & Yun Hang Hu
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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 AccessEngraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect
Allogeneic iPSC-derived cartilage organoids survive and integrate with surrounding native cartilage without immune reactions in a primate model of chondral defects in the knee joints, being remodeled and functioning as articular cartilage.
- Kengo Abe
- , Akihiro Yamashita
- & Noriyuki Tsumaki
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Article
| Open AccessAcoustic metamaterials-driven transdermal drug delivery for rapid and on-demand management of acute disease
Treating acute disease like anaphylaxis is challenging due to the inability to administer therapeutics in a timely manner and regulate pharmacokinetics precisely within a short time window. Here the authors develop active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management.
- Junhua Xu
- , Hongwei Cai
- & Feng Guo
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Article
| Open AccessBioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation
Bioengineered livers using decellularized scaffolds have been considered as an alternative to donor organs. Here, the authors modulate biophysical properties of decellularized scaffolds by crosslinking with nano-graphene oxide, thereby greatly enhancing therapeutic efficacy of bioengineered livers.
- Da-Hyun Kim
- , Min-Ji Kim
- & Kyung-Sun Kang
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Article
| Open AccessA cooperative nano-CRISPR scaffold potentiates immunotherapy via activation of tumour-intrinsic pyroptosis
Delivery of immune therapy drugs to tumours might be hampered by their limited bioavailability and the difficulty of targeting complex exogenous compounds. Here authors trigger immunologic cell death, via activating tumour-cell-intrinsic pathways via CRISPR-based nanotechnology to enable efficient anti-tumour immune response in mouse models of melanoma.
- Ning Wang
- , Chao Liu
- & Changyang Gong
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Article
| Open AccessNanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells
Mesenchymal Stromal Cells are hard to expand whilst retaining immunomodulatory properties due to spontaneous differentiation and ageing in culture. Here, the authors describe a mechanotransductive link between metabolism and functional activity and identify bioactive metabolites to expand functional MSCs at cell therapy scale.
- Ewan A. Ross
- , Lesley-Anne Turner
- & Matthew J. Dalby
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Perspective
| Open AccessMedical microrobots in reproductive medicine from the bench to the clinic
Microrobotics is an emerging technology with wide implications for medical fields, such as assisted reproduction. Here the authors show how the key challenges regarding materials, processes and engineering as well as ethical and regulatory implications can be addressed towards a clinical adoption.
- Richard Nauber
- , Sandhya R. Goudu
- & Mariana Medina-Sánchez
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Article
| Open AccessLight-driven biological actuators to probe the rheology of 3D microtissues
The mechanical properties of biological tissues are key to their integrity and function. Here, the authors engineer 3D microtissues from optogenetically modified fibroblasts and use light to quantify tissue elasticity and strain propagation using their own constituent cells as internal actuators.
- Adrien Méry
- , Artur Ruppel
- & Thomas Boudou
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Article
| Open AccessUltra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection
In this study, the authors developed an ultra-long-acting injectable, biodegradable, and removable in-situ forming implant delivering cabotegravir (CAB ISFI). CAB ISFI was well tolerated and protected against multiple rectal SHIV challenges in female macaques.
- Isabella C. Young
- , Ivana Massud
- & S. Rahima Benhabbour
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Article
| Open AccessEngineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation
Antigen-specific tolerance represents a promising strategy to treat type 1 diabetes and islet allograft rejection. Here, the authors deliver immune signals to lymph nodes to promote antigen-specific regulatory T cells and prevent disease in models of type 1 diabetes and allogenic islet transplantation.
- Joshua M. Gammon
- , Sean T. Carey
- & Christopher M. Jewell
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Article
| Open AccessNew insights in polydopamine formation via surface adsorption
Polydopamine is a biomimetic self-adherent polymer, which can be easily deposited on a wide variety of materials but the polymerization mechanism and the key intermediate species formed during the deposition process are still controversial. Here, the authors report a systematic investigation of polydopamine formation on halloysite nanotubes.
- Hamoon Hemmatpour
- , Oreste De Luca
- & Petra Rudolf
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Article
| Open AccessMacromolecular sheets direct the morphology and orientation of plate-like biogenic guanine crystals
Animals precisely control the morphology and assembly of guanine crystals to produce diverse optical phenomena but little is known about how organisms regulate crystallization to produce optically useful morphologies. Here, the authors demonstrate that pre-assembled, fibrillar sheets in developing scallop eyes template nucleation and direct the growth and orientation of plate-like guanine crystals showing a striking resemblance to melanosome morphogenesis.
- Avital Wagner
- , Alexander Upcher
- & Benjamin A. Palmer
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Article
| Open AccessTautomerism unveils a self-inhibition mechanism of crystallization
Modifiers of diverse materials exhibit structures or compositions that differ from a solute molecule but often contain similar functional motifs that facilitate molecular recognition for modifier binding to crystal surfaces. Here the authors examine the intrinsic capability of tautomers, or structural isomers, to operate as crystal growth inhibitors.’
- Weiwei Tang
- , Taimin Yang
- & Jeffrey D. Rimer
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Article
| Open AccessEnhancing CAR-T cell functionality in a patient-specific manner
‘Manufacturing CAR-T cells is a streamlined and highly regulated procedure involving T-cell-expansion and activation on a standardised platform. Here, the authors show that a personalized approach, taking the phenotypic attributes of individual patients’ T cells into account, leads to more efficient CAR-T cell manufacturing and better CAR-T cell functionality.
- David K. Y. Zhang
- , Kwasi Adu-Berchie
- & David J. Mooney
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Article
| Open AccessHydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands
Injectable biomimetic hydrogels hold significant promise for tissue engineering applications. Here, the authors present a hybrid myoglobin:peptide hydrogel to overcome a critical oxygen shortage following neural stem cell transplantation, thus increasing cell survival and integration.
- Y. Wang
- , E. R. Zoneff
- & D. R. Nisbet
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Article
| Open AccessBiomolecular condensates formed by designer minimalistic peptides
The molecular mechanisms underlying the formation of biomolecular condensates have not been fully elucidated. Here the authors show that the LLPS propensity, dynamics, and encapsulation efficiency of designed peptide condensates can be tuned by subtle changes to the peptide composition.
- Avigail Baruch Leshem
- , Sian Sloan-Dennison
- & Ayala Lampel
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Article
| Open AccessA natural biological adhesive from snail mucus for wound repair
Natural adhesives have received a lot of attention recently. Here, the authors develop a natural biological adhesive from snail mucus that can adhere to wet tissue and be used to accelerate healing of skin wounds.
- Tuo Deng
- , Dongxiu Gao
- & Mingyi Wu
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Article
| Open AccessBioprinting microporous functional living materials from protein-based core-shell microgels
Extrusion bioprinting can be used to produce living materials but controlling cell microenvironments is challenging. Here, the authors use a type of core-shell microgel ink that decouples cell culture from material processing to produce functional materials with a range of potential applications.
- Yangteng Ou
- , Shixiang Cao
- & Tuomas P. J. Knowles
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Article
| Open AccessStem cell–nanomedicine system as a theranostic bio-gadolinium agent for targeted neutron capture cancer therapy
Gadolinium-neutron capture therapy (Gd-NCT) in glioblastoma shows promise but is limited by toxicity and short-half life in the brain. Here, the authors present a magnetised stem cell-nanoparticle system to facilitate brain penetrance of Gd-NCT and demonstrate its utility in an orthotopic rat glioblastoma model.
- Yen-Ho Lai
- , Chia-Yu Su
- & San-Yuan Chen
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Article
| Open AccessAn integrated Mg battery-powered iontophoresis patch for efficient and controllable transdermal drug delivery
Wearable transdermal iontophoresis offers advantages for patient-comfort when deploying epidermal diseases treatments but current self-powered iontophoresis based on energy harvesters is limited in the support of efficient long-term operation therapeutic administration. Here, the authors propose a simplified wearable iontophoresis patch with a built-in Mg battery for efficient and controllable transdermal delivery.
- Yan Zhou
- , Xiaoteng Jia
- & Gordon Wallace
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Article
| Open AccessLigand-tethered lipid nanoparticles for targeted RNA delivery to treat liver fibrosis
Gene delivery to fibroblasts for liver fibrosis treatment remains challenging. Here the authors develop a combinatorial library of ligand-tethered lipidoids via a modular synthetic method and adopt a 2-round screening strategy to identify lipidoids for potent and selective gene delivery to fibroblasts.
- Xuexiang Han
- , Ningqiang Gong
- & Michael J. Mitchell