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| Open AccessSurface chemistry-mediated modulation of adsorbed albumin folding state specifies nanocarrier clearance by distinct macrophage subsets
Polymeric nanocarriers used for drug delivery are often coated by albumin in vivo influencing the therapeutic outcomes. Here, the authors engineer the surface chemistry of a nanocarrier to either stabilize or denature the structure of adsorbed albumin, resulting in evasion or clearance by macrophages.
- Michael P. Vincent
- , Sharan Bobbala
- & Evan A. Scott
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Article
| Open AccessNanoscale characterization of the biomolecular corona by cryo-electron microscopy, cryo-electron tomography, and image simulation
Understanding the biomolecular corona is of key importance to nanomedicine. Here, the authors report on cryo-electron and tomographic imaging of the corona formed on model nanoparticles and the 3D reconstruction of the corona to study the distribution and association of the biomolecules with the nanoparticle.
- Sara Sheibani
- , Kaustuv Basu
- & Morteza Mahmoudi
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Article
| Open AccessA hybrid semiconducting organosilica-based O2 nanoeconomizer for on-demand synergistic photothermally boosted radiotherapy
Tumor hypoxia is a major limitation in radiotherapy, and strategies to address this often fail due to high oxygen consumption. Here, the authors report a nanomaterial assembly for the simultaneous reduction in mitochondrial respiration and to supply oxygen to potentiate radiotherapy.
- Wei Tang
- , Zhen Yang
- & Xiaoyuan Chen
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Article
| Open AccessNanohole-boosted electron transport between nanomaterials and bacteria as a concept for nano–bio interactions
Nanomaterials have attracted attention as antibacterial agents and have several modes of action. Here, the authors report on 2D transition metal disulphide nanosheets with hole boosted electron donation/withdrawal for enhanced antibacterial and biofilm activity caused by electron damage.
- Tonglei Shi
- , Xuan Hou
- & Xiangang Hu
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Article
| Open AccessCarbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance
The transmembrane P-glycoprotein (P-gp) pumps are known to promote drug resistance by enhancing drug efflux. Here, the authors deliver P-gp inhibitor and a chemotherapeutic agent using tumor blood vessel-targeting nanoparticle, to overcome drug resistance.
- Hai Wang
- , Yutong Liang
- & Xiaoming He
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Article
| Open AccessRemote near infrared identification of pathogens with multiplexed nanosensors
Fast and specific detection of pathogenic bacteria is needed to combat infections. Here the authors generate an array of near-infrared biosensors based on carbon nanotubes to detect released metabolites and virulence factors and use them to distinguish pathogens such as S. aureus and P. aeruginosa.
- Robert Nißler
- , Oliver Bader
- & Sebastian Kruss
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Article
| Open AccessPolycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window
Stimuli-responsive nanomaterials offer the opportunity to exploit nanoscale cooperativity to improve the precision of diagnostic or therapeutic outcomes. Here, the authors report the design, synthesis and characterization of a series of degradable ultra-pH sensitive polymers that amplify small acidic pH changes to efficacious therapeutic outputs.
- Xu Wang
- , Jonathan Wilhelm
- & Jinming Gao
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Review Article
| Open AccessEngineering microrobots for targeted cancer therapies from a medical perspective
Microbot delivery devices are the latest development in attempts to overcome the systemic toxicity associated with classical chemotherapy. Here, the authors review the recent progress in the field with a focus on the clinical translation and potential of the research and give a future perspective on this topic.
- Christine K. Schmidt
- , Mariana Medina-Sánchez
- & Oliver G. Schmidt
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Article
| Open AccessTargeted scavenging of extracellular ROS relieves suppressive immunogenic cell death
Reactive oxygen species in the tumour microenvironment can have an immunosuppressive effect. Here, the authors devise a nanoparticle that anchors to the extracellular matrix within tumours and scavenges reactive oxygen species, resulting in an enhanced immune response within the tumour.
- Hongzhang Deng
- , Weijing Yang
- & Xiaoyuan Chen
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Article
| Open AccessHybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis
The application of STING agonists and the blockade of the SIRPα–CD47 signaling axis are emerging immunotherapeutic strategies. Here the authors show that hybrid cellular membrane nanovesicles loaded with a STING agonist or overexpressing high-affinity SIRPα variants can be exploited to promote anti-tumor immune responses.
- Lang Rao
- , Lei Wu
- & Xiaoyuan Chen
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Article
| Open AccessCombinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions
Multivalent ligand-receptor interactions enhance binding selectivity in biological systems, and may be exploited to design synthetic systems. Here the authors demonstrate a multivalent behavior where the ability to bind the target occurs when the receptor density is within a specific range.
- Meng Liu
- , Azzurra Apriceno
- & Stefano Angioletti-Uberti
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Article
| Open AccessPharmacophore hybridisation and nanoscale assembly to discover self-delivering lysosomotropic new-chemical entities for cancer therapy
Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here, the authors generate single-drug nanoparticles by hybridising lysomotropic detergents and the bisaminoquinoline-based autophagy inhibitor, and show their therapeutic potential as autophagy-inhibition based combination therapy.
- Zhao Ma
- , Jin Li
- & Yuanpei Li
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Article
| Open AccessIntratumoral generation of photothermal gold nanoparticles through a vectorized biomineralization of ionic gold
Intracellular generation of gold nanoparticles has drawn attention but toxic effects have limited potential applications. Here, the authors report on the delivery of ionic gold with PEG resulting in faster synthesis and reduced toxicity due to lower concentrations of ionic gold required and explore potential applications.
- Aaron S. Schwartz-Duval
- , Christian J. Konopka
- & Dipanjan Pan
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Article
| Open AccessUse of ratiometrically designed nanocarrier targeting CDK4/6 and autophagy pathways for effective pancreatic cancer treatment
Aberrant cell cycle machinery and loss of the CDKN2A tumor suppressor locus make CDK4/6 a potential target in pancreatic ductal adenocarcinoma (PDAC). Here, the authors use ratiometrically designed nanoparticles to codeliver the CDK4/6 inhibitor palbociclib and the autophagy inhibitor hydroxychloroquine, and show their synergistic therapeutic effects in mouse model of PDAC.
- Ying Ji
- , Xiangsheng Liu
- & Huan Meng
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Article
| Open AccessEnhancing chemotherapy response through augmented synthetic lethality by co-targeting nucleotide excision repair and cell-cycle checkpoints
Cell cycle checkpoint kinase, MK2, is in synthetic relationship with p53 in the DNA damage response to chemotherapeutic agents. Here, the authors report XPA as a third gene in which simultaneous targeting of MK2 and XPA further enhances sensitivity to cisplatin in p53-deficient tumours.
- Yi Wen Kong
- , Erik C. Dreaden
- & Michael B. Yaffe
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Article
| Open AccessPhotothermogenetic inhibition of cancer stemness by near-infrared-light-activatable nanocomplexes
Cancer stem cells (CSCs) are known to induce chemotherapy resistance, and cause tumour relapse and metastasis. Here, the authors develop photoactive nanocarbon complexes with second near-infrared photothermal ability to target cancer cells overexpressing the receptor TRPV2 and show it to suppress CSCs through dysregulation of the Wnt/β-catenin signalling pathway.
- Yue Yu
- , Xi Yang
- & Eijiro Miyako
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Article
| Open AccessMagnetic field boosted ferroptosis-like cell death and responsive MRI using hybrid vesicles for cancer immunotherapy
The immune system can eradicate tumours, and several chemotherapy strategies have been reported to augment the immune system. Here, the authors report an exogenous magnetic field triggered strategy to boost Ferroptosis-like death and endow responsive MRI by using a biosafe hybrid core-shell vesicle for cancer therapy.
- Bo Yu
- , Bongseo Choi
- & Dong-Hyun Kim
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Article
| Open AccessLight-triggered switching of liposome surface charge directs delivery of membrane impermeable payloads in vivo
Surface charge plays an important role in determining nanoparticle fate in vivo. Here the authors report on the development of a light triggered charge switching liposome and demonstrate light triggered liposome targeting, uptake and payload delivery in a zebrafish model.
- Gabriela Arias-Alpizar
- , Li Kong
- & Frederick Campbell
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Article
| Open AccessUltrasmall copper-based nanoparticles for reactive oxygen species scavenging and alleviation of inflammation related diseases
Oxidative stress is involved in several diseases and is a target for intervention. Here, the authors report on the synthesis of ultrasmall copper-based nanozymes as reactive oxygen species scavengers and demonstrate improved treatment outcomes in acute liver and kidney injury and wound healing in vivo.
- Tengfei Liu
- , Bowen Xiao
- & Jun Deng
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Article
| Open AccessContrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis in mouse models of type1 diabetes
Infiltration of immune cells to the pancreatic islets precedes clinical symptoms of type 1 diabetes, and lack of methods to detect this insulitis impedes early interventions. Here the authors report a contrast enhanced ultrasound method that can detect early insulitis in mouse models of type 1 diabetes, based on increased microvascular permeability.
- David G. Ramirez
- , Eric Abenojar
- & Richard K. P. Benninger
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Article
| Open AccessTransformable hybrid semiconducting polymer nanozyme for second near-infrared photothermal ferrotherapy
Due to tumour microenvironment, Fenton reactions have low therapeutic efficiency. Here the authors report on the application of NIR-II hybrid semiconducting nanozymes for combined photothermal therapy and enhanced ferrotherapy with photoacoustic imaging and show application in vivo in tumour models.
- Yuyan Jiang
- , Xuhui Zhao
- & Ruiping Zhang
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Article
| Open AccessExtracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping
Expression of Cas9 and gRNA from viral vectors in vivo may cause off-target activity. Here the authors present NanoMEDIC, which uses nanovesicles to transiently deliver editing machinery to hard-to-transfect cells.
- Peter Gee
- , Mandy S. Y. Lung
- & Akitsu Hotta
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Article
| Open AccessChemotaxis-driven delivery of nano-pathogenoids for complete eradication of tumors post-phototherapy
The presence of several biological barriers impede the efficacy of nano-mediated drug delivery for solid cancer therapy. Here, the authors develop a nano-pathogenoid system that targets circulating neutrophils and show that it overcomes these biological barriers and improves tumour targeting and efficacy.
- Min Li
- , Shuya Li
- & Yucai Wang
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Article
| Open AccessDual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors
The exclusion of cytotoxic T cells remains an important barrier to the efficacy of immunotherapies. Here the authors demonstrate that the combination anti-fibrosis agents and immune-enhanced cytokines can enhance T cell infiltration in a mouse model of pancreatic cancer.
- Yukun Huang
- , Yu Chen
- & Jun Chen
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Article
| Open AccessSelf-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor
The hypoxic microenvironment in solid tumors limits the efficacy of photodynamic therapy (PDT) since oxygen is necessary to produce high cytotoxic singlet oxygen species. Here, the authors develop an improved self-assembled single-atom nanozyme which allows oxygen generation to enhance PDT efficacy.
- Dongdong Wang
- , Huihui Wu
- & Yanli Zhao
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Article
| Open AccessTailoring the component of protein corona via simple chemistry
The interaction between proteins and nanomaterials is complex and of interest for controlling nanoparticle fate. Here, using experimental and computational methods, the authors report on the effect of hydroxyl groups on protein interaction and how they can be used to enhance circulation times.
- Xiang Lu
- , Peipei Xu
- & Yu-Qiang Ma
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Article
| Open AccessFusion dynamics of cubosome nanocarriers with model cell membranes
Understanding the fusion of nanocarriers with cell membranes is important to the design of effective drug delivery methods. Here, the authors report on a study into the fusion of cubosomes with model cell membranes underflow conditions and report on the binding kinetics.
- Brendan P. Dyett
- , Haitao Yu
- & Charlotte E. Conn
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Article
| Open AccessEndogenous stimulus-powered antibiotic release from nanoreactors for a combination therapy of bacterial infections
Endogenous triggered delivery of antibiotics over an external triggered delivery has distinct advantages. Here, the authors report on a nanoreactor triggered by bacterial toxin to trigger a drug release mechanism and capture the toxin for reduced toxicity of toxins and improved immune response.
- Yang Wu
- , Zhiyong Song
- & Heyou Han
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Article
| Open AccessNear-infrared light and tumor microenvironment dual responsive size-switchable nanocapsules for multimodal tumor theranostics
Nanoparticles that can change shape have attracted attention for improved circulation and tumor penetration. Here, the authors report on a size changeable nanoparticle that responds to near-infrared light and can be used for photothermal therapy, photodynamic therapy, and drug delivery applications.
- Zhiyi Wang
- , Yanmin Ju
- & Yanglong Hou
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Article
| Open AccessInhibition of amyloid beta toxicity in zebrafish with a chaperone-gold nanoparticle dual strategy
Treating Alzheimer’s disease, one of the most common neurodegenerative diseases, is of wide interest. Here, the authors report on the development of casein coated gold nanoparticles which were able to cross the blood brain barrier and protect against amyloid beta toxicity in a zebrafish model.
- Ibrahim Javed
- , Guotao Peng
- & Sijie Lin
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Article
| Open AccessInterplay of protein corona and immune cells controls blood residency of liposomes
Protein corona formation is known to have significant effects upon nanomaterials application. Here, the authors investigate the creation of a protein coating on liposomes with the aim of improving liposome circulation time by avoiding leukocyte capture and demonstrated application in vitro and ex vivo.
- Francesca Giulimondi
- , Luca Digiacomo
- & Giulio Caracciolo
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Article
| Open AccessBrain-targeted drug delivery by manipulating protein corona functions
Plasma proteins may severely affect the in vivo performance of liposomes. Here, the authors develop bio-inspired liposomes that specifically absorb brain-targeted apolipoproteins and preserve their bioactivities, thereby achieving efficient brain targeting with minor influence on immunocompatibility of liposomes.
- Zui Zhang
- , Juan Guan
- & Changyou Zhan
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Article
| Open AccessCryoprotectant enables structural control of porous scaffolds for exploration of cellular mechano-responsiveness in 3D
Cellular responses to mechanical stimulation have emerged as an important area of research. Here, the authors use cryoprotectant to control the pore size and mechanical properties of porous scaffolds without changing the scaffold composition to allow for the study of cellular mechano-responsiveness in 3D.
- Shumeng Jiang
- , Cheng Lyu
- & Yanan Du
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Article
| Open AccessBioinspired lipoproteins-mediated photothermia remodels tumor stroma to improve cancer cell accessibility of second nanoparticles
The stromal cells and extracellular matrix hamper nanoparticle access to cancer cells and their anti-cancer efficacy. Here, the authors report a bioinspired lipoprotein (bLP) for photothermal remodelling of tumour stroma and show this to improve subsequent bLP accessibility to cancer cells.
- Tao Tan
- , Haiyan Hu
- & Yaping Li
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Article
| Open AccessProbing the impact of sulfur/selenium/carbon linkages on prodrug nanoassemblies for cancer therapy
Prodrug-based self-assembled nanoparticles have emerged as an efficient drug delivery system (DDS) for cancer therapy. Here, the authors show that the type of bond in prodrug assemblies influences the efficiency of the DDS on several different levels.
- Bingjun Sun
- , Cong Luo
- & Jin Sun
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Article
| Open AccessRelaxin gene delivery mitigates liver metastasis and synergizes with check point therapy
Activated hepatic stellate cells are associated with fibrosis and liver metastases. Here, the authors identify an endogenous role of relaxin in regulating the activation of hepatic stellate cells and report nanoparticle-mediated relaxin gene therapy to mitigate fibrosis and liver metastasis.
- Mengying Hu
- , Ying Wang
- & Leaf Huang
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Article
| Open AccessThe origin of heterogeneous nanoparticle uptake by cells
Cellular uptake of nanoparticles is highly variable between individual cells in a population. Here, the authors show that this heterogeneity is a result of varying numbers of nanoparticle-containing endosomes while the nanoparticle dose per endosome remains constant.
- Paul Rees
- , John W. Wills
- & Huw D. Summers
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Article
| Open AccessAlbumin tailoring fluorescence and photothermal conversion effect of near-infrared-II fluorophore with aggregation-induced emission characteristics
There is a balance between the fluorescence and photothermal properties of fluorescent molecules. Here, the authors report on an NIR-II fluorophore which binds with human serum albumin changing the equilibrium, increasing the photothermal efficiency, and demonstrate application of this for tumour ablation.
- Shuai Gao
- , Guoguang Wei
- & Wei Lu
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Article
| Open AccessCheckpoint blockade and nanosonosensitizer-augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice
Immunotherapy for the treatment of cancer can be complicated by side effects and poor efficacy. Here, the authors use a nanoparticle-based approach in combination with a TLR7 agonist and sonodynamic therapy, and find that when used together with anti-PD-L1, tumour formation and metastases are impacted.
- Wenwen Yue
- , Liang Chen
- & Yu Chen
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Article
| Open AccessLiver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases
Berberine has lipid-lowering effects and other metabolic benefits, but it presents with poor bioavailability. Here the authors conjugate berberine to liver-targeting nanoparticles, and show increased accumulation of berberine in the liver, improved metabolic profiles and reduced atherosclerotic plaques in mice.
- Hui-Hui Guo
- , Chen-Lin Feng
- & Jian-Dong Jiang
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Article
| Open AccessMultispectral optoacoustic imaging of dynamic redox correlation and pathophysiological progression utilizing upconversion nanoprobes
Reactive oxygen (ROS) and nitrogen (RNS) species are involved in key physiological processes and their balance is altered in various human diseases. Here the authors develop near-infrared upconversion nanoprobes to screen ROS/RNS dynamics simultaneously by multispectral optoacoustic imaging in vivo.
- Xiangzhao Ai
- , Zhimin Wang
- & Bengang Xing
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Article
| Open AccessA biomimetic nanoreactor for synergistic chemiexcited photodynamic therapy and starvation therapy against tumor metastasis
Photodynamic therapy is usually ineffective against deeply seated metastatic tumors due to poor penetration of the excitation light. Here, the authors design a biomimetic nanoreactor which can convert nutriment glucose into toxic singlet oxygen via chemiluminescence resonance energy transfer with no light excitation and demonstrate its high efficacy in a mouse lung metastatic model.
- Zhengze Yu
- , Ping Zhou
- & Bo Tang
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Article
| Open AccessEstablishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics
Nanoparticle applications are limited by insufficient understanding of physiochemical properties on in vivo disposition. Here, the authors explore the influence of size, surface chemistry and administration on the biodisposition of mesoporous silica nanoparticles using image-based pharmacokinetics.
- Prashant Dogra
- , Natalie L. Adolphi
- & C. Jeffrey Brinker
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Article
| Open AccessCloaking nanoparticles with protein corona shield for targeted drug delivery
The efficacy of nanoparticles can be significantly inhibited by serum proteins binding to them. Here, the author developed a supramolecularly constructed protein corona on nanoparticles, which minimises interactions with serum proteins to prevent the clearance of these particles by macrophages.
- Jun Yong Oh
- , Han Sol Kim
- & Ja-Hyoung Ryu
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Article
| Open AccessCell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes
Therapeutic alteration of protein expression using modified mRNA is limited by immunogenicity and instability in vivo. Here the authors use antibody-coated lipid nanoparticles to deliver mRNA to leukocytes and drive expression of anti-inflammatory cytokines in an inflammatory bowel disease mouse model.
- Nuphar Veiga
- , Meir Goldsmith
- & Dan Peer
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Article
| Open AccessNanoscale metal-organic frameworks for mitochondria-targeted radiotherapy-radiodynamic therapy
Photosensitizers delivered to mitochondria of cancer cells can enhance photodynamic therapy. Here, the authors report mitochondria-targeted radiation therapy and radiodynamic therapy of colorectal cancer models with a cationic nanoscale metal-organic framework to overcome shallow light penetration of Ru-based photosensitizers.
- Kaiyuan Ni
- , Guangxu Lan
- & Wenbin Lin
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Article
| Open AccessCationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation
Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here the authors use ~40 nm cationic nanoparticles to scavenge cfDNA, and demonstrate the potential for nanomedicine to relieve debilitating RA symptoms.
- Huiyi Liang
- , Bo Peng
- & Yongming Chen
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Article
| Open AccessHarnessing copper-palladium alloy tetrapod nanoparticle-induced pro-survival autophagy for optimized photothermal therapy of drug-resistant cancer
“Conventional chemotherapy-photothermal therapy combination has limited efficacy in drug resistant cancers. Here they develop Copper-palladium tetrapod nanoparticles to overcome these challenges and show them to work in synergy with autophagy inhibitors to treat drug resistant cancers”
- Yunjiao Zhang
- , Rui Sha
- & Long-ping Wen
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Article
| Open AccessLocal generation of hydrogen for enhanced photothermal therapy
The tracking and targeted release of multi-agents to cooperatively treat cancer is a developing and evolving field. Here, the authors demonstrate the anticancer effects of cubic Pd hydride nanocrystals with photoacoustic imaging properties that can release hydrogen under an NIR trigger and have photothermal effects.
- Penghe Zhao
- , Zhaokui Jin
- & Qianjun He