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| Open AccessTechnical challenges of studying the impact of plasma components on the efficacy of lipid nanoparticles for vaccine and therapeutic applications
- Jens B. Simonsen
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Review Article
| Open AccessCritical learning from industrial catalysis for nanocatalytic medicine
The knowledge gained from industrial catalysis benefits advancements of nanocatalytic medicines. Here the authors review the similarities, differences and connections in catalytic reactions between industrial and medical applications to support deep understanding and rational design of nanocatalytic medicines.
- Zhaokui Jin
- , Lingdong Jiang
- & Qianjun He
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Article
| Open AccessExosome-coated oxygen nanobubble-laden hydrogel augments intracellular delivery of exosomes for enhanced wound healing
Challenges including hypoxia, inflammation, and inadequate exosome intracellular delivery hinder wound healing. Here, the authors show that a multifunctional exosome-coated oxygen nanobubble-laden hydrogel enhances exosome delivery and mitigates hypoxia for enhanced wound healing.
- Xiaoxue Han
- , Chaimongkol Saengow
- & Joseph Irudayaraj
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Article
| Open AccessOxygen-independent organic photosensitizer with ultralow-power NIR photoexcitation for tumor-specific photodynamic therapy
Conventional photodynamic therapy (PDT) is hindered by oxygen-dependent photosensitization pathways and high-power-density photoexcitation. Here, the authors develop polymer-based organic photosensitizers (PSs) through PS skeleton design and side-chain engineering to allow tumor-specific PDT under oxygen-free conditions using ultralow-power 808 nm photoexcitation.
- Yufu Tang
- , Yuanyuan Li
- & Bin Liu
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Article
| Open AccessLanthanide luminescence nanothermometer with working wavelength beyond 1500 nm for cerebrovascular temperature imaging in vivo
The strong scattering of biological tissue causes challenges when monitoring temperature changes at the microscale. Here, the authors propose a nanothermometer based on lanthanide luminescence, enabling minimally invasive imaging of the cerebrovascular system of mice at nearly 200 μm resolution.
- Yukai Wu
- , Fang Li
- & Xingjun Zhu
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Article
| Open AccessCholesterol-modified sphingomyelin chimeric lipid bilayer for improved therapeutic delivery
Cholesterol (Chol) transfer from lipid bilayer jeopardizes membrane stability and causes premature payload leakage, yielding suboptimal efficacy. Here, the authors report a Chol-modified sphingomyelin (SM) bilayer via covalently conjugating Chol to SM, which retains Chol condensing ability and improves pharmacokinetics and therapeutic delivery of various drugs in diverse disease animal models.
- Zhiren Wang
- , Wenpan Li
- & Jianqin Lu
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Article
| Open AccessMesoporous nanoperforators as membranolytic agents via nano- and molecular-scale multi-patterning
Plasma membrane lysis is an effective anticancer strategy that mostly relies on soluble molecular membranolytic agents, while nanomaterial-based membranolytic agents have been unexplored. Herein, the authors report a nano- and molecular-scale multi-patterning strategy for fabricating mesoporous membranolytic nanoperforators with an intrinsic membranolytic activity.
- Yannan Yang
- , Shiwei Chen
- & Chengzhong Yu
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Article
| Open AccessTargeted delivery of Fc-fused PD-L1 for effective management of acute and chronic colitis
Triggering the PD-1/PD-L1 immune checkpoint is an attractive therapeutic approach in inflammatory bowel disease, and PD-L1, conjugated to the Fc part of an immunoglobulin (PD-L1-Fc) has been shown to be effective in mouse models. Here authors show that fusing to reactive oxygen species (ROS)-responsive nanoparticles improves effect of PD-L1-Fc due to targeting to inflammation sites, while systemic toxicity is reduced.
- Xudong Tang
- , Yangyang Shang
- & Lei Chen
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Article
| Open AccessUltrasmall metal alloy nanozymes mimicking neutrophil enzymatic cascades for tumor catalytic therapy
Emulating the killing function of neutrophils, which involves the enzymatic cascade of superoxide dismutase (SOD) and myeloperoxidase (MPO), is promising for cancer therapy, but developing SOD-MPO cascade in one nanozyme is challenging. Here the authors report ultrasmall AuPd alloy nanozymes that mimic neutrophil enzymatic cascades for catalytic treatment of tumors.
- Xiangqin Meng
- , Huizhen Fan
- & Kelong Fan
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Article
| Open AccessNon-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and viral vaccines
Different approaches have been described for the transdermal delivery of drugs. Here the authors report the design of a fluorocarbon modified chitosan-based non-invasive transdermal platform for the delivery of biomacromolecules, such as viral antigens for vaccines or immune checkpoint inhibitors for melanoma immunotherapy.
- Wenjun Zhu
- , Ting Wei
- & Zhuang Liu
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Article
| Open AccessLithiated porous silicon nanowires stimulate periodontal regeneration
Prelithiation can introduce controllable amounts of lithium within porous silicon, however it yields a highly reactive material unsuitable for biomedicine. In this study, the authors present a strategy to lithiate porous silicon nanowires, resulting in a biocompatible and bioresorbable material.
- Martti Kaasalainen
- , Ran Zhang
- & Ciro Chiappini
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Article
| Open AccessInjectable hydrogel electrodes as conduction highways to restore native pacing
No preventive treatment addresses the underlying condition that leads to cardiac arrest. Here, researchers developed an injectable hydrogel electrode that achieves pacing that mimics physiological conduction with the potential to eliminate lethal arrhythmias and provide painless defibrillation.
- Gabriel J. Rodriguez-Rivera
- , Allison Post
- & Elizabeth Cosgriff-Hernandez
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Article
| Open AccessA light-activatable theranostic combination for ratiometric hypoxia imaging and oxygen-deprived drug activity enhancement
Monitoring the level of hypoxia in a tumour is of use when treating by chemotherapy or photodynamic therapy, but can be challenging. Here, the authors report the development of a theranostic combination for light activated hypoxia imaging and modulation, and prodrug activation.
- Lei Ge
- , Yikai Tang
- & Xiqun Jiang
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Article
| Open AccessNanomedicine-based co-delivery of a calcium channel inhibitor and a small molecule targeting CD47 for lung cancer immunotherapy
Lung cancer is characterized by an immunosuppressive microenvironment, limiting responses to immunotherapies. Here the authors report the design of a pH-responsive nanomedicine for the co-delivery of a T-type calcium channel inhibitor and of a small molecule targeting CD47, promoting anti-tumor immune responses in orthotopic lung cancer preclinical models.
- Yuedong Guo
- , Qunqun Bao
- & Jianlin Shi
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Article
| Open AccessSphingomyelin-derived nanovesicles for the delivery of the IDO1 inhibitor epacadostat enhance metastatic and post-surgical melanoma immunotherapy
Epacadostat is a selective IDO1 inhibitor shown to promote anti-tumor immune responses in preclinical models, however it has failed in a Phase III clinical trial for treating metastatic melanoma. Here the authors design a sphingomyelin-derived nanovesicle system for epacadostat delivery with improved pharmacokinetics and anti-tumor activity when combined with a PD-1 inhibitor in melanoma preclinical models.
- Zhiren Wang
- , Wenpan Li
- & Jianqin Lu
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Article
| Open AccessPathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke
Reperfusion is a main strategy for restoring blood supply after ischemic stroke, but it induces neuroinflammation that undergoes dynamic progression, hindering the treatment of ischemic stroke. Here, the authors report a pathogenesis-adaptive nanosystem for sequential and on-demand regulation of reperfusion-induced dynamic neuroinflammation for ischemic stroke therapy.
- Di Wu
- , Jing Zhou
- & Zhong Chen
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Article
| Open AccessNanosensitizer-mediated augmentation of sonodynamic therapy efficacy and antitumor immunity
The dense stroma of desmoplastic tumor limits nanotherapeutic penetration and hampers the antitumor immune response. Here the authors use tin monosulfide nanoparticles as nano-sonosensitizers to overcome the stromal barrier in triple negative breast cancer and improve the efficacy of sonodynamic therapy and boost antitumor immunity.
- Yongjiang Li
- , Wei Chen
- & Wei Tao
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Article
| Open AccessAdaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer
There is an emerging interest in the use of mRNA therapeutics in cancer treatment, but their precise in vivo delivery remains a challenge. Here the authors develop IFN-γ mRNA-loaded small extracellular vesicles (sEVs) with CD64 overexpressed on their surface and demonstrate its efficacy in glioblastoma mouse models resistant to immunotherapy.
- Shiyan Dong
- , Xuan Liu
- & Wen Jiang
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Article
| Open AccesspH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy
A high abundance of tumour associated macrophages with immunosuppressive properties is associated with inefficient anti-tumour immune responses. Here the authors report the design and characterization of pH-gated nanoparticles selectively targeting and reprogramming M2-like macrophages in the tumour microenvironment, re-sensitizing tumours to immune checkpoint blockade.
- Mingmei Tang
- , Binlong Chen
- & Yiguang Wang
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Article
| Open AccessCell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy
Tumor associated macrophages (TAMs) contribute to the immunosuppressive tumor microenvironment, including hepatocellular carcinoma (HCC). Here the authors show that macrophage-derived microparticles modified with a M2-like macrophage targeting peptide and loaded with the TLR7/8 agonist resiquimod reprogram TAMs from immunosuppressive to inflammatory, promoting anti-tumor immune responses in preclinical HCC models.
- Xiaoqiong Zhang
- , Zhaohan Wei
- & Lu Gan
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Article
| Open AccessTheranostic imaging and multimodal photodynamic therapy and immunotherapy using the mTOR signaling pathway
Approaches to combine photodynamic therapy (PDT) with immunotherapy are emerging, allowing the treatment of primary and metastatic tumors. Here the authors report the design and characterization of a nanomaterial for theranostic imaging and photodynamic therapy eliciting anti-tumor immune response in preclinical cancer models.
- Huiling Zhou
- , Dongsheng Tang
- & Haihua Xiao
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Article
| Open AccessBiosynthesized gold nanoparticles that activate Toll-like receptors and elicit localized light-converting hyperthermia for pleiotropic tumor immunoregulation
Bacteria have been exploited as a potential bio-factory for the synthesis of nanoparticles. Here the authors report the generation of gold nanoparticles from Escherichia coli and show their application for eliciting hyperthermia and anti-tumor immune responses in preclinical cancer models.
- Hao Qin
- , Yang Chen
- & Ruifang Zhao
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Article
| Open AccessCholesterol removal improves performance of a model biomimetic system to co-deliver a photothermal agent and a STING agonist for cancer immunotherapy
Strategies for biological membrane engineering have been proposed to enhance their anti-clearance efficiency and improve their clinical translation potential. Here the authors design nanoparticles coated with low-cholesterol membranes from T cells overexpressing PD1, showing reduced clearance in the blood and improved anti-tumor efficacy when loaded with a STING agonist and a photothermal agent.
- Lin Li
- , Mengxing Zhang
- & Ling Zhang
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Article
| Open AccessHyaluronic acid-bilirubin nanomedicine-based combination chemoimmunotherapy
Immunosuppressive tumour immune microenvironments (TME) limit the success of immune checkpoint blockade (ICD). Here, the authors develop a hyaluronic acid-bilirubin nanoparticle (HABN) capable of inducing immunogenic cell death in tumour cells and altering the TME, resulting in increased sensitivity to ICB (anti-PD-L1) in preclinical models of colorectal cancer and breast cancer.
- Yonghyun Lee
- , Jongyoon Shinn
- & James J. Moon
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Article
| Open AccessPrussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments
Chemodynamic therapy (CDT) uses Fenton chemistry to covert hydrogen peroxide in cancer cells to toxic hydroxyl radicals, but endogenous hydrogen peroxide is insufficient to drive sustainable CDT. Here, the authors report a water oxidation CoFe Prussian blue nanoframe to provide sustained, external energy free self-supply of hydroxyl radicals for CDT.
- Liu-Chun Wang
- , Pei-Yu Chiou
- & Chen-Sheng Yeh
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Article
| Open AccessPhotothermia at the nanoscale induces ferroptosis via nanoparticle degradation
Iron oxide magnetic nanoparticles are utilized in Fe(II)-induced ferroptosis for cancer therapy, but controlling the Fe(II) release from magnetic nanoparticles remains challenging. Here the authors reveal that photothermia at the nanoscale can remotely trigger the degradation of magnetic nanoparticles, leading to Fe(II) release and a synergistic photothermo-ferroptotic therapy.
- Alexandre Fromain
- , Jose Efrain Perez
- & Claire Wilhelm
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Article
| Open AccessGeneration of whole tumor cell vaccine for on-demand manipulation of immune responses against cancer under near-infrared laser irradiation
Whole autologous tumor cell vaccine (TCV) has been proposed as a tool for cancer immunotherapy. Here the authors describe the design of a TCV platform based on photothermal nanoparticle-loaded tumor cells, triggering NIR laser irradiation induced anti-tumor immune responses at the vaccination site.
- Jiaqi Meng
- , Yanlin Lv
- & Wei Wei
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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 AccessAntioxidant hepatic lipid metabolism can be promoted by orally administered inorganic nanoparticles
Inorganic nanoparticles can accumulate in living organisms causing a dose-dependent increase in cellular reactive oxygen species. Here, the authors leverage this as a potential scheme for regulating metabolic disorders, showing that that low-dose nanoparticle administration can enhance lipid hydrolysis and alleviate fatty liver.
- Jie Cai
- , Jie Peng
- & Diming Wang
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Article
| Open AccessNanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy
Targeting the TGF-β signaling pathway has been exploited to relieve immunosuppression in the tumor microenvironment. Here the authors describe the design of a nanoplatform integrating the TGF-β receptor 1 inhibitor LY2157299 and the ROS-responsive JQ1 pro-drug, promoting anti-tumor immune responses in preclinical cancer models.
- Mengxue Zhou
- , Jiaxin Wang
- & Haijun Yu
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Article
| Open AccessTemperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis
Treatment of the chronic disease ulcerative colitis is impeded by systemic side effects of orally administered drugs. Here the authors develop a gel that uses the rectal temperature as a mechanism to trigger solidification for localized delivery of colitis therapeutics.
- Marianna Carone
- , Marianne R. Spalinger
- & Simone Aleandri
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Article
| Open AccessGas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation
Gas-based therapy is an emerging therapeutic option for cancer treatment. Here the authors design a virus-mimicking hollow mesoporous tetrasulfide-doped organosilica for co-encapsulation of an aggregation-induced emission (AIE)-active luminogen and manganese carbonyl to fabricate a STING activating gas nano-adjuvant for photo-immunotherapy, promoting anti-tumor immune response in preclinical models.
- Kaiyuan Wang
- , Yang Li
- & Xiaoyuan Chen
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Article
| 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 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 AccessModular-designed engineered bacteria for precision tumor immunotherapy via spatiotemporal manipulation by magnetic field
Several strategies have been employed to enhance the tumor-targeting and anti-cancer properties of engineered bacteria. Here the authors describe the design of alternating magnetic field-manipulated bacteria engineered to release an anti-CD47 nanobody, promoting anti-tumor immune response in preclinical cancer models.
- Xiaotu Ma
- , Xiaolong Liang
- & Guangjun Nie
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Article
| Open AccessMechano-boosting nanomedicine antitumour efficacy by blocking the reticuloendothelial system with stiff nanogels
Nanomedicine proofed to be efficient in cancer therapy but rapid clearance from blood circulation by reticuloendothelial system (RES) severely limits the antitumor efficacy. Here, the authors design a series of nanogels with distinctive stiffness and investigate how nanogel mechanical properties could be leveraged to overcome RES.
- Zheng Li
- , Yabo Zhu
- & Zifu Li
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Article
| Open AccessControlled sequential in situ self-assembly and disassembly of a fluorogenic cisplatin prodrug for cancer theranostics
Manipulating molecular self-assembly and disassembly in vivo may permit temporal control of drug delivery and release. Here, the authors report a fluorogenic cisplatin prodrug for cancer theranostics by leveraging stimuli-triggered in situ self-assembly and intracellular disassembly processes.
- Xidan Wen
- , Rui Zhang
- & Deju Ye
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Article
| Open AccessMolecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke
Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide but current drug therapeutics show important limitations. Here, the authors exploit a selfpropelling nano-penetrator with high fuel loading and controllable motion which is molecularly co-assembled using a photothermal photosensitizer and a photothermal-activable NO donor.
- Hongyuan Zhang
- , Zhiqiang Zhao
- & Cong Luo
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Article
| Open AccessNear-infrared-IIb emitting single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown after traumatic brain injury
Monitoring the status of blood-brain barrier (BBB) and inhibiting reactive oxygen species (ROS)-mediated oxidative damage are key issues in the treatment of traumatic brain injury (TBI). Here, the authors design a near-infrared-IIb emitting Mn single-atom catalyst for imaging-guided therapy to alleviate ROS mediated neuroinflammation in the brain and simultaneously obtain timely feedback of therapeutic effect, promoting the reconstruction of BBB and recovery of neurological function after TBI in mice.
- Biao Huang
- , Tao Tang
- & Ran Cui
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Article
| Open AccessA pH-responsive T1-T2 dual-modal MRI contrast agent for cancer imaging
Magnetic resonance imaging (MRI) is a well-established non-invasive medical imaging technology. Here, to improve the performance of the technique, the authors describe the design of a pH-responsive T1-T2 dual-modal MRI contrast agent, showing enhanced imaging sensitivity in preclinical cancer models.
- Hongwei Lu
- , An Chen
- & Leilei Tian
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Article
| Open AccessUltrasensitive rapid cytokine sensors based on asymmetric geometry two-dimensional MoS2 diodes
Detection of cytokine biomarkers has the potential to aid in diagnosis and treatment of different diseases. Here, the authors report on the creation of an asymmetric geometry MoS2 diode-based biosensor for the detection of TNF-α as a model biomarker in a proof of concept study.
- Thushani De Silva
- , Mirette Fawzy
- & Michael M. Adachi
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Article
| Open AccessMagnesium hexacyanoferrate nanocatalysts attenuate chemodrug-induced cardiotoxicity through an anti-apoptosis mechanism driven by modulation of ferrous iron
Doxorubicin is commonly used in cancer chemotherapy, but its cardiotoxicity from iron overload is one of the severe side effects. Here, the authors prepare magnesium hexacyanoferrate nanocatalysts to capture excess ferrous species and eliminate cytotoxic radical species in vitro and in vivo.
- Minfeng Huo
- , Zhimin Tang
- & Jianlin Shi
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Article
| Open AccessAtomically dispersed golds on degradable zero-valent copper nanocubes augment oxygen driven Fenton-like reaction for effective orthotopic tumor therapy
Single-atom catalysts emerge as nanocatalytic medicine in chemodynamic therapy but suffer from inefficient kinetics for the production of reactive oxygen species because of the cell’s antioxidative mechanisms. Here, the authors employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatment.
- Liu-Chun Wang
- , Li-Chan Chang
- & Chen-Sheng Yeh
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Article
| Open AccessA nuclease-mimetic platinum nanozyme induces concurrent DNA platination and oxidative cleavage to overcome cancer drug resistance
One of the mechanisms underlying platinum (Pt) resistance is the spontaneous nucleotide-excision repair of cancer cells. Here, nuclease-mimetic Pt nanozymes are targeted to the cancer cell nucleus and induce concurrent DNA platination and oxidative cleavage to overcome Pt resistance.
- Fangyuan Li
- , Heng Sun
- & Daishun Ling
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Article
| Open AccessHybrid chalcogen bonds in prodrug nanoassemblies provides dual redox-responsivity in the tumor microenvironment
While homodimeric prodrug assemblies can improve drug loading and limit toxicity in cancer therapy, bioactivation within the target site is limited. Here, the authors introduce a hybrid chalcogen bond linker to a docetaxel dimeric prodrug nanoassembly and demonstrate its improved selfassembly, redox-responsivity and antitumor efficacy.
- Tian Liu
- , Lingxiao Li
- & Jin Sun
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Article
| Open AccessMicrofluidic vortex focusing for high throughput synthesis of size-tunable liposomes
Liposomes are widely used in pharmaceuticals yet trade-offs between uniform size and mass production, limit production and application. Here, the authors report on the design of a microfluidic vortex focusing microfluidic technique which can mass produce liposomes with controlled size and low variability.
- Jung Yeon Han
- , Joseph N. La Fiandra
- & Don L. DeVoe
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Article
| Open AccessFlash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment
Achieving the delivery of drugs into the centre of solid tumours is a challenge due to the tumour micro-environment. Here, the authors propose a system for using the rapid release of large quantities of drug inside tumour microcapillaries for the gradient-driven diffusion of drugs into solid tumours.
- Ivan V. Zelepukin
- , Olga Yu. Griaznova
- & Andrei V. Zvyagin
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Article
| Open AccessLigand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy
Displaying the correct surface functionality at the right time is important for efficient drug delivery. Here, the authors report on the pH-responsive, sequential presentation of cell-penetrating peptide and liver-targeting moiety designed to improve intestinal absorption and liver targeting and demonstrate this with insulin delivery in vivo.
- Tiantian Yang
- , Aohua Wang
- & Yong Gan
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Article
| Open AccessMeasurements of heterogeneity in proteomics analysis of the nanoparticle protein corona across core facilities
Analysis of the protein corona formed around nanoparticles is important for multiple applications in nanomedicine, the methods used at core facilities used for analysis can impact the results. Here, the authors report on a study into the variability of the results obtained from 17 different core facilities and the implications of this.
- Ali Akbar Ashkarran
- , Hassan Gharibi
- & Morteza Mahmoudi