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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
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Article
| Open AccessProgrammable self-regulated molecular buffers for precise sustained drug delivery
Natural buffer molecules ensure the controlled and precise delivery of specific molecules in biology. Here, the authors replicate the natural buffer systems using aptamers with controlled binding efficiency to control and maintain the levels of free drugs both in vitro and in vivo.
- Arnaud Desrosiers
- , Rabeb Mouna Derbali
- & Alexis Vallée-Bélisle
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Article
| Open AccessSystematic design of cell membrane coating to improve tumor targeting of nanoparticles
Surface modification of nanoparticles by cell membrane (CM) coating to improve their bio-interface properties often results in partial coating. Here the authors show that partial coating is an intermediate state due to the absorption of CM fragments or vesicles and can be resolved by increasing CM fluidity with external phospholipids.
- Lizhi Liu
- , Dingyi Pan
- & Vesa-Pekka Lehto
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Article
| Open AccessPhotocatalytic glucose depletion and hydrogen generation for diabetic wound healing
Hydrogenation is a treatment for chronic inflammation caused by high glucose levels in diabetic ulcers, However, current therapies have limitations. Here, the authors report on the creation of a visible light photocatalytic agent which depletes glucose in the wound and generates hydrogen to aid in diabetic wound healing.
- Shengqiang Chen
- , Yanxia Zhu
- & Qianjun He
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Article
| Open AccessPayload distribution and capacity of mRNA lipid nanoparticles
Lipid nanoparticles (LNPs) are effective vehicles to deliver mRNA vaccines and therapeutics but assessing the mRNA packaging characteristics in LNPs is challenging. Here, the authors report that mRNA and lipid contents in LNP formulations can be quantitatively examined by multi-laser cylindrical illumination confocal spectroscopy at the single-nanoparticle level.
- Sixuan Li
- , Yizong Hu
- & Hai-Quan Mao
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Article
| Open AccessBacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy
Different blood-brain barrier permeable systems, such as bacteria loaded with chemotherapy, have been proposed to treat glioblastoma. Here, the authors generate bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles to eliminate bacteria-infected glioblastoma cells and induce an anti-tumour immune response upon photothermal therapy.
- Rong Sun
- , Mingzhu Liu
- & Yao He
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Article
| Open AccessHighly hydrated paramagnetic amorphous calcium carbonate nanoclusters as an MRI contrast agent
Sensitive, biocompatible and stable contrast agents for MRI are in demand. Here, the authors combine gadolinium ions with amorphous calcium carbonate to make stable paramagnetic amorphous carbonate nanoclusters with high MRI contrast and significantly improved biocompatibility over commercial gadolinium-based agents.
- Liang Dong
- , Yun-Jun Xu
- & Shu-Hong Yu
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Article
| Open AccessAdenosine triphosphate-activated prodrug system for on-demand bacterial inactivation and wound disinfection
Prodrugs are increasingly promising in tackling bacterial resistance and efficacy of treatment. Here, the authors encapsulated horseradish peroxidase and zeolitic imidazolate framework-8 loaded with indole-3-acetic acid in polyacrylamide hydrogel microspheres for ATP-activated wound disinfection.
- Yuhao Weng
- , Huihong Chen
- & Hongliang Tan
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Article
| Open AccessBiomimetic material degradation for synergistic enhanced therapy by regulating endogenous energy metabolism imaging under hypothermia
Metal organic frameworks (MOF) coated with mammalian cell membranes have good biocompatibility. Here, the authors develop a cobalt based hydrogen sulphide producing MOF cloaked with a macrophage membrane and show that the subsequent system can reduce tumour growth in mice.
- Kai Cheng
- , Bo Liu
- & Yuan-Di Zhao
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Article
| Open AccessCancer immune therapy using engineered ‛tail-flipping’ nanoliposomes targeting alternatively activated macrophages
Tumor-associated macrophages are mostly pro-tumorigenic, due to their re-programming by the tumor microenvironment. Here authors show that nanoliposomes, incorporating phospholipids with a flipping-tail chain, are engulfed specifically by intratumoral, alternatively activated macrophages, while delivering a cargo that converts these cells into anti-tumor macrophages.
- Praneeth R. Kuninty
- , Karin Binnemars-Postma
- & Jai Prakash
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Article
| Open AccessTPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia
Overproduction of efflux pumps represents an important mechanism of Klebsiella pneumonia resistance to tigecycline. Here, the authors design TPGS- and S-thanatin functionalized nanorods loaded with tigecycline to increase drug accumulation inside bacteria and overcome bacterial resistance.
- Xiaojuan Wang
- , Xiaoling Xu
- & Saiping Jiang
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Article
| Open AccessCatalytical nano-immunocomplexes for remote-controlled sono-metabolic checkpoint trimodal cancer therapy
Ultrasound-based therapies in combination with immune checkpoint blockade have been shown to improve the efficacy of cancer immunotherapy. Here the authors report the design of a pH-responsive and sono-irradiation activatable nanosystem functionalized with anti-PD-L1 and adenosine deaminase for sono-metabolic cancer immunotherapy.
- Chi Zhang
- , Jingsheng Huang
- & Kanyi Pu
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Article
| Open AccessEfficient aqueous remote loading of peptides in poly(lactic-co-glycolic acid)
Encapsulation of bioactive peptides in slow-release particles is complex and relies on organic solvents. Here, the authors absorb peptides in a polymer phase from water, creating a simple low-cost encapsulation process in a class of polymer depot.
- Morgan B. Giles
- , Justin K. Y. Hong
- & Steven P. Schwendeman
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Article
| Open AccessCatalytic activity imperative for nanoparticle dose enhancement in photon and proton therapy
Nanoparticles have recently received attention in radiation therapy since they can act as radioenhancers. In this article, the authors report on the dose enhancement capabilities of a series of nanoparticles based on their metal core composition and beam characteristics, obtaining designing criteria for their optimal performance in specific radiotreatments.
- Lukas R. H. Gerken
- , Alexander Gogos
- & Inge K. Herrmann
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Article
| Open AccessNanoparticle-enhanced radiotherapy synergizes with PD-L1 blockade to limit post-surgical cancer recurrence and metastasis
Tumor recurrence after surgical resection is associated with a poor clinical outcome. Here the authors design a manganese dioxide-based nanosystem to increase response to radio-immunotherapy by relieving tumor hypoxia and targeting myeloid cells, showing reduced post-surgical cancer recurrence and metastasis.
- Xin Guan
- , Liping Sun
- & Wenwen Yue
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Article
| Open AccessReversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts
Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment. Here, in preclinical cancer models, the authors show that PTT efficacy could be improved using tumor cell-derived microparticles that co-deliver the photosensitizer indocyanine green and a vitamin-D receptor ligand, calcipotriol, resulting in tumor extracellular matrix remodelling and ameliorated anti-tumor immune responses.
- Xin Li
- , Tuying Yong
- & Xiangliang Yang
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Article
| Open AccessA bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway
One common cause of vision loss after retinal detachment surgery is retinal scarring. Here the authors demonstrate that a bio-functional polymer can prevent retinal scarring by suppression of epithelial-mesenchymal transition and hyper-proliferation of retinal pigment epithelial cells.
- Bhav Harshad Parikh
- , Zengping Liu
- & Xinyi Su
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Article
| Open AccessFibronectin binding protein B binds to loricrin and promotes corneocyte adhesion by Staphylococcus aureus
The first step during skin colonization by is its adhesion to corneocytes. Da Costa et al. show that the cell wall-anchored fibronectin binding protein B (FnBPB) of S. aureus binds to loricrin. Applying single cell force spectroscopy, they demonstrate that this interaction promotes adhesion of S. aureus to human corneocytes.
- Thaina M. da Costa
- , Albertus Viljoen
- & Joan A. Geoghegan
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Article
| Open AccessProtective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury
Pharmacological interventions against hepatic ischemia-reperfusion injury remain limited. Here, the authors provide a nanotherapeutics-based solution combining reactive oxygen species scavenging and nitric oxide modulation.
- Jing Mu
- , Chunxiao Li
- & Xiaoyuan Chen
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Article
| Open AccessGolgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy
Aggregation induced emission luminogen (AIEgen) based photosensitizers (PSs) have been developed for photodynamic cancer therapy. Here the authors report a series of AIEgen-based PSs that selectively target the Golgi apparatus, showing enhanced singlet oxygen generation and photodynamic therapy performance in cancer models.
- Minglun Liu
- , Yuncong Chen
- & Zijian Guo
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Article
| Open AccessBioorthogonal in situ assembly of nanomedicines as drug depots for extracellular drug delivery
Delivering the correct concentration of drugs to the correct location is a challenge in cancer therapy. Here, the authors generate a drug loaded nanoparticle that enlarges following contact with the internal tumour cell environment, resulting in the retention of the nanoparticle and loaded drugs in cancer cells.
- Ziyang Cao
- , Dongdong Li
- & Xianzhu Yang
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Article
| Open AccessConstruction of a two-dimensional artificial antioxidase for nanocatalytic rheumatoid arthritis treatment
Inflammatory diseases such as rheumatoid arthritis are associated with high reactive oxygen species levels. Here, the authors report on 2D metal-organic frameworks as an artificial antioxidase with the same manganese coordination centre as two natural enzymes, and demonstrate their anti-inflammatory effects and anti-arthritic effects in vivo.
- Bowen Yang
- , Heliang Yao
- & Jianlin Shi
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Article
| Open AccessFibroblast activation protein activated antifibrotic peptide delivery attenuates fibrosis in mouse models of liver fibrosis
Activated hepatic stellate cells contribute towards the pathogenesis of liver fibrosis, and overexpress fibroblast activation protein. Here the authors report a targeted peptide-delivery system in which fibroblast activation protein liberates the antifibrotic peptide melittin, and demonstrate the approach attenuates fibrosis in mouse models of liver fibrosis.
- Jaiwoo Lee
- , Junho Byun
- & Yu-Kyoung Oh
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Article
| Open AccessMicroalgae-based oral microcarriers for gut microbiota homeostasis and intestinal protection in cancer radiotherapy
Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Here the authors use a natural microalga to readily construct an oral delivery system to achieve effective radioprotection for the small intestine.
- Dongxiao Zhang
- , Danni Zhong
- & Min Zhou
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Article
| Open AccessHigh drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury
High drug loading improves therapeutic efficacy and reduces side effects in drug delivery. Here, the authors use controlled diffusion of solvents to precipitate drug nanoparticles in polymer particles while the polymer is solidifying and demonstrate the particles for drug delivery in a spinal cord injury model.
- Wei Li
- , Jian Chen
- & Dongfei Liu
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Article
| Open AccessCombining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy
The p53 tumor suppressor gene is frequently mutated in liver cancer. Here the authors show that restoration of p53 expression with a mRNA nanoparticle platform elicits anti-tumor immune responses and promotes response to immune checkpoint blockade in preclinical models of p53-null hepatocellular carcinoma.
- Yuling Xiao
- , Jiang Chen
- & Jinjun Shi
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Article
| Open AccessDegradable mesoporous semimetal antimony nanospheres for near-infrared II multimodal theranostics
The properties of mesoporous nanomaterials have been exploited for several applications, including drug delivery and NIR-II photoacoustic imaging. Here, the authors design monodispersed semimetallic mesoporous antimony nanospheres with photothermal conversion efficiency in the second near-infrared range and drug loading capacity, showing their potential for cancer photothermal/chemo therapy.
- Yu Chen
- , Zhongzheng Yu
- & Junle Qu
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Article
| Open AccessInterfacial-confined coordination to single-atom nanotherapeutics
Developing single atom systems with improved catalytic potential for bio-application has major therapeutic potential. Here, the authors report on the development of a metal single-atom on a carbon dot support confined within mesoporous silica for the development of therapeutic agents.
- Limei Qin
- , Jie Gan
- & Jianlin Shi
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Article
| Open AccessTheranostic near-infrared-IIb emitting nanoprobes for promoting immunogenic radiotherapy and abscopal effects against cancer metastasis
Hypoxia and immunosuppression contribute to tumor resistance to radiotherapy (RT). Here the authors design a nanoprobe based on NIR-IIb emitting quantum dots for image-guided RT and modified with catalase to relieve hypoxia in the tumor microenvironment, enhancing the precision and efficacy of RT and promoting anti-tumor immune responses.
- Hao Li
- , Meng Wang
- & Zhi-Jun Sun
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Article
| Open AccessGold nanoparticles enhance antibody effect through direct cancer cell cytotoxicity by differential regulation of phagocytosis
Antibody therapies have huge potential in treating cancer but currently suffer from problems with delivery. Here the authors report on a study into then conjugation of Ramucirumab to gold nanoparticles to improve delivery and add theranostic capabilities, demonstrating preferential toxicity in gastric cancer cells.
- Linyang Fan
- , Weizhi Wang
- & Minzhi Zhao
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Article
| Open AccessMOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload
Targeting damage to mitochondria has become an effective strategy antitumor therapies. Here, the authors report on nanoagents with upconversion nanoparticles as cores and photoacid-loaded MOFs as shells for NIR triggered Fenton reaction, acidification and calcium overload to provide synergistic mitochondrial damage.
- Weier Bao
- , Ming Liu
- & Zhiyuan Tian
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Article
| Open AccessHedgehog artificial macrophage with atomic-catalytic centers to combat Drug-resistant bacteria
The increase in drug-resistant bacteria is a world-wide health issue that demands the development of alternatives to standard antibiotic treatments. In this study, the authors synthesise a hedgehog artificial macrophage with heme-mimetic catalytic centres, and peroxidase- and haloperoxidase-mimicking activities, for the treatment of methicillin-resistant Staphylococcus aureus.
- Yanping Long
- , Ling Li
- & Changsheng Zhao
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Article
| Open AccessHigh-spatial and colourimetric imaging of histone modifications in single senescent cells using plasmonic nanoprobes
The authors demonstrate a colourimetric imaging method using plasmonic nanoparticles for visualisation of heterochromatin histone markers. Based on the distance-dependent coupling effect, resulting in spectral shifts, they observe reorganisation of histone markers caused by oncogene-induced senescence.
- Hyun Ji An
- , Yun Kim
- & Inhee Choi
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Article
| Open AccessCell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles
Cell membrane coating of nanomaterials has become an attractive method of improving targeting, residence and biocompatibility. Here, the authors demonstrated that most nanoparticles are only partially coated by standard methods, and show the coating degree can impact the biological fate of nanoparticles.
- Lizhi Liu
- , Xuan Bai
- & Vesa-Pekka Lehto
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Article
| Open AccessTransformation of tenofovir into stable ProTide nanocrystals with long-acting pharmacokinetic profiles
Antiretroviral therapy (ART) for the treatment of HIV-1 requires life-long daily adherence to supress viral replication, and nucleoside reverse transcriptase inhibitors that are commonly used in ART have not been converted into long-acting agents. Here, the authors report two lipophilic tenofovir (TVF) ProTide nanoformulations, NM1TFV and NM2TFV, which sustain drug levels above therapeutic concentrations for two months after a single intramuscular dose in rats.
- Denise A. Cobb
- , Nathan Smith
- & Benson Edagwa
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Comment
| Open AccessThe need for robust characterization of nanomaterials for nanomedicine applications
Robust and precise characterization of the interactions between nanoengineered materials and biosystems is vital for the development of safe, efficient diagnostic and therapeutic nanomedicines. This comment discusses the key aspects of nanoparticle characteristics affecting the interpretation of nano-bio interface data.
- Morteza Mahmoudi