Publications by authors named "Chunying Chen"

319 Publications

Death Pathways of Cancer Cells Modulated by Surface Molecule Density on Gold Nanorods.

Adv Sci (Weinh) 2021 Sep 15:e2102666. Epub 2021 Sep 15.

Department of Nanomedicine & International Joint Cancer Institute, Naval Medical University, Shanghai, 200433, China.

Necrosis induces strong inflammation with undesirable implications in clinics compared with apoptosis. Fortunately, the switch between necrosis and apoptosis could be realized by tailoring the appropriate structural properties of gold nano rods (GNRs) that could precisely modulate cell death pathways. Herein, the intracellular interaction between GNRs and organelles is monitored and it is found that lysosomes dominates necrosis/apoptosis evoking. Then the surface molecule density of GNRs, which is first defined as ρ (N /(a × π × Diameter × Length)), mediates lysosome activities as the membrane permeabilization (LMP), the Cathepsin B and D release, the cross-talk between lysosome and different organelles, which selectively evokes apoptosis or necrosis and the production of TNF-α from macrophages. GNRs with small ρ mainly induce apoptosis, while with large ρ they greatly contribute to necrosis. Interestingly, necrosis can be suppressed by GNRs with higher ρ due to the overexpression of key protease caspase 8, which cleaves the RIP1-RIP3 complex and activates caspase 3 followed by necrosis to apoptosis transition. This investigation indicates that the ρ greatly affects the utility of nanomaterials and different structural properties of nanomaterials have different implications in clinics.
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http://dx.doi.org/10.1002/advs.202102666DOI Listing
September 2021

A One-pot-synthesized Double-layered Anticoagulant Hydrogel Tube.

Chem Res Chin Univ 2021 Sep 4:1-7. Epub 2021 Sep 4.

GBA Research Innovation Institute for Nanotechnology, Guangzhou, 510700 P. R. China.

Extracorporeal membrane oxygenation(ECMO) has emerged as a viable treatment in severe cases of acute respiratory distress syndrome, acute respiratory failure, and adult respiratory distress syndrome. However, thromboembolic events stemming from the use of ECMO devices results in significant morbidity and mortality rates; the inner surface of the ECMO tubing comes into contact with the blood and can readily initiate coagulation. In addition, the tubing needs to be continually replaced due to thromboses on the inner tube wall, which not only increases the risk of infection but also the economic burden. Despite considerable effort, a surface modification strategy that effectively addresses these challenges has not yet been realized. In this study, we developed an integrated hollow core-shell-shell hydrogel tube of gelatin/alginate/acrylamide-bacterial nanocellulose(GAA) that meets the anticoagulant requirements for the inner tubing layer as well as the highly elastic soft material needed for the outer layer. Using static blood from healthy volunteers, we confirmed that the platelets or coagulation is not stimulated by the GAA tubing. Importantly, experiments with dynamic blood also demonstrated that the inner layer of the tubing does not elicit blood clotting. The one-pot-synthesized process may provide guidance for the design of anticoagulation tubes used clinically.

Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s40242-021-1267-3.
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http://dx.doi.org/10.1007/s40242-021-1267-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418287PMC
September 2021

Biodegradation of graphdiyne oxide in classically activated (M1) macrophages modulates cytokine production.

Nanoscale 2021 Aug 23;13(30):13072-13084. Epub 2021 Jul 23.

Nanosafety & Nanomedicine Laboratory (NNL), Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Graphdiyne oxide (GDYO) is a carbon-based nanomaterial possessing sp and sp-hybridized carbon atoms with many promising applications. However, its biocompatibility and potential biodegradability remain poorly understood. Using human primary monocyte-derived macrophages as a model we show here that GDYO elicited little or no cytotoxicity toward classically activated (M1) and alternatively activated (M2) macrophages. Moreover, GDYO reprogrammed M2 macrophages towards M1 macrophages, as evidenced by the elevation of specific cell surface markers and cytokines and the induction of NOS2 expression. We could also show inducible nitric oxide synthase (iNOS)-dependent biodegradation of GDYO in M1 macrophages, and this was corroborated in an acellular system using the peroxynitrite donor, SIN-1. Furthermore, GDYO elicited the production of pro-inflammatory cytokines in a biodegradation-dependent manner. Our findings shed new light on the reciprocal interactions between GDYO and human macrophages. This is relevant for biomedical applications of GDYO such as the re-education of tumor-associated macrophages or TAMs.
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http://dx.doi.org/10.1039/d1nr02473fDOI Listing
August 2021

A Titanium Nitride Nanozyme for pH-Responsive and Irradiation-Enhanced Cascade-Catalytic Tumor Therapy.

Angew Chem Int Ed Engl 2021 Aug 28. Epub 2021 Aug 28.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, University of Chinese Academy of Sciences, Beijing, 100190, China.

Nanozyme-based catalytic tumor therapy is an emerging therapeutic method with high reactivity in response to tumor microenvironments (TMEs). To overcome the current limitations of deficient catalytic activity of nanozymes, we studied the contributing factors of enzymatic activity based on non-metallic-atom doping and irradiation. Nitrogen doping significantly enhanced the peroxidase activity of Ti-based nanozymes, which was shown experimentally and theoretically. Based on the excellent NIR-adsorption-induced surface plasmon resonance and photothermal effect, the enzymatic activity of TiN nanoparticles (NPs) was further improved under NIR laser irradiation. Hence, an acidic TME-responsive and irradiation-mediated cascade nanocatalyst (TLGp) is presented by using TiN-NP-encapsulated liposomes linked with pH-responsive PEG-modified glucose oxidase (GOx). The integration of pH-responsive GOx-mediated H O self-supply, nitrogen-doping, and irradiation-enhanced enzymatic activity of TiN NPs and mild-photothermal therapy enables an effective tumor inhibition by TLGp with minimal side effects in vivo.
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http://dx.doi.org/10.1002/anie.202106750DOI Listing
August 2021

Heterojunction of Vertically Arrayed MoS Nanosheet/N-Doped Reduced Graphene Oxide Enabling a Nanozyme for Sensitive Biomolecule Monitoring.

Anal Chem 2021 08 3;93(32):11123-11132. Epub 2021 Aug 3.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, University of Chinese Academy of Sciences, Beijing 100190, China.

Enzymes are still indispensable for bio-assaying methods in biomolecule detection by far. The unsatisfied long-term instability, high cost, and susceptibility to the physical environment of natural enzymes are obvious weak points. Here, we developed peroxidase-like heterostructured nanozyme, vertically arraying molybdenum disulfide nanosheets on a substrate layer of nitrogen-doped reduced graphene oxide (MoS/N-rGO), with a well-pleasing stability that is characterized by the retained enzymatic activity and maintained structure after 2 years of casual storage at ambient temperatures or 80 cycles of catalytic reaction. The catalytic kinetics of the as-prepared heterostructured nanozyme was superior to some reported nanozymes and even horse radish peroxidase, which was demonstrated due to the defect-rich MoS with Mo and S vacancies and nitrogen-doped rGO experimentally and theoretically. The vertically heterostructured nanozyme exhibited adequate analytical performance in sensitive and quantitative detection of glucose and glutathione (GSH), with a large dynamic sensing range and extremely low limit of detection (0.02 and 0.12 μM (3σ/slope) for glucose and GSH, respectively). We hope this inspired artificial nanozyme will contribute to the future development in sensitive detection of other biomolecules in physiological conditions.
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http://dx.doi.org/10.1021/acs.analchem.1c01550DOI Listing
August 2021

The Underlying Function and Structural Organization of the Intracellular Protein Corona on Graphdiyne Oxide Nanosheet for Local Immunomodulation.

Nano Lett 2021 07 9;21(14):6005-6013. Epub 2021 Jul 9.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.

Nanomaterial-biology interaction is the critical step in the fate of biomedical nanomedicines, influencing the consequent biological outcomes. Herein, we present two-dimensional carbon-based nanomaterials-graphdiyne oxide (GDYO) nanosheets that interact with an intracellular protein corona consisting of signal transducer and activator of transcription 3 (STAT3), inducing the reeducation of immunosuppressive macrophages. The interaction at the GDYO-STAT3 interface, driven by structure matching, hydrogen bonding, and salt bridges, simultaneously triggers the immune response in the tumor microenvironment, facilitating cancer immunotherapy. For the first time, our data reveal an interaction mechanism between the nanoparticle-protein interfaces inevitably formed inside the cells that determines the macrophage phenotype. Our results suggest that GDYO nanosheets could be applied for local immunomodulation due to their function and structural organization of the intracellular protein corona occurred inside macrophages.
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http://dx.doi.org/10.1021/acs.nanolett.1c01048DOI Listing
July 2021

Advances in versatile anti-swelling polymer hydrogels.

Mater Sci Eng C Mater Biol Appl 2021 Aug 27;127:112208. Epub 2021 May 27.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, PR China. Electronic address:

Swelling is ubiquitous for traditional as-prepared hydrogels, but is unfavorable in many situations, especially biomedical applications, such as tissue engineering, internal wound closure, soft actuating and bioelectronics, and so forth. As the swelling of a hydrogel usually leads to a volume expansion, which not only deteriorates the mechanical property of the hydrogel but can bring about undesirable oppression on the surrounding tissues when applied in vivo. In contrast, anti-swelling hydrogels hardly alter their volume when applied in aqueous environment, therefore reserving the original mechanical performance and size-stability and facilitating their potential application. In the past decade, with the development of advanced hydrogels, quite a number of anti-swelling hydrogels with versatile functions have been developed by researchers to meet the practical applications well, through integrating anti-swelling property with certain performance or functionality, such as high strength, self-healing, injectability, adhesiveness, antiseptics, etc. However, there has not been a general summary with regard to these hydrogels. To promote the construction of anti-swelling hydrogels with desirable functionalities in the future, this review generalizes and analyzes the tactics employed so far in the design and manufacture of anti-swelling hydrogels, starting from the viewpoint of classical swelling theories. The review will provide a relatively comprehensive understanding of anti-swelling hydrogels and clues to researchers interested in this kind of materials to develop more advanced ones suitable for practical application.
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http://dx.doi.org/10.1016/j.msec.2021.112208DOI Listing
August 2021

Tailoring metal-organic frameworks-based nanozymes for bacterial theranostics.

Biomaterials 2021 08 4;275:120951. Epub 2021 Jun 4.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China; GBA National Institute for Nanotechnology Innovation, Guangdong, 510700, China. Electronic address:

Nanozymes are next-generation artificial enzymes having distinguished features such as cost-effective, enhanced surface area, and high stability. However, limited selectivity and moderate activity of nanozymes in the biochemical environment hindered their usage and encouraged researchers to seek alternative catalytic materials. Recently, metal-organic frameworks (MOFs) characterized by distinct crystalline porous structures with large surface area, tunable pores, and uniformly dispersed active sites emerged, that filled the gap between natural enzymes and nanozymes. Moreover, by selecting suitable metal ions and organic linkers, MOFs can be designed for effective bacterial theranostics. In this review, we briefly presented the design and fabrication of MOFs. Then, we demonstrated the applications of MOFs in bacterial theranostics and their safety considerations. Finally, we proposed the major obstacles and opportunities for further development in research on the interface of nanozymes and MOFs. We expect that MOFs based nanozymes with unique physicochemical and intrinsic enzyme-mimicking properties will gain broad interest in both fundamental research and biomedical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120951DOI Listing
August 2021

Hypoxia and pH co-triggered oxidative stress amplifier for tumor therapy.

Eur J Pharmacol 2021 Aug 25;905:174187. Epub 2021 May 25.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing, 100021, PR China. Electronic address:

To keep fast proliferation, tumor cells are exposed to higher oxidative stress than normal cells and they upregulate the amount of some antioxidants such as glutathione (GSH) against reactive oxygen species to maintain the balance. This phenomenon is severe in hypoxic tumor cells. Although researchers have proposed a series of treatment strategies based on regulating the intracellular reactive oxygen species level, few of them are related to the hypoxic tumor. Herein, a novel organic compound (PLC) was designed by using lysine as a bridge to connect two functional small molecules, a hypoxia-responsive nitroimidazole derivative (pimonidazole) and a pH-responsive cinnamaldehyde (CA) derivative. Then, the oxidative stress amplifying ability of PLC in hypoxic tumor cells was evaluated. The acidic microenvironment of tumor can trigger the release of CA to produce reactive oxygen species. Meanwhile, large amount of nicotinamide adenine dinucleotide phosphate (NADPH) can be consumed to decrease the synthesis of GSH during the bio-reduction process of the nitro group in PLC under hypoxic conditions. Therefore, the lethal effect of CA can be amplified for the decrease of GSH. Our results prove that this strategy can significantly enhance the therapeutic effect of CA in the hypoxic tumor cells.
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http://dx.doi.org/10.1016/j.ejphar.2021.174187DOI Listing
August 2021

Multifunctional Graphdiyne-Cerium Oxide Nanozymes Facilitate MicroRNA Delivery and Attenuate Tumor Hypoxia for Highly Efficient Radiotherapy of Esophageal Cancer.

Adv Mater 2021 Jun 5;33(24):e2100556. Epub 2021 May 5.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, China.

Radioresistance is an important challenge for clinical treatments. The main causes of radioresistance include hypoxia in the tumor microenvironment, the antioxidant system within cancer cells, and the upregulation of DNA repair proteins. Here, a multiple radiosensitization strategy of high-Z-element-based radiation enhancement is designed, attenuating hypoxia and microRNA therapy. The novel 2D graphdiyne (GDY) can firmly anchor and disperse CeO nanoparticles to form GDY-CeO nanocomposites, which exhibit superior catalase-mimic activity in decomposing H O to O to significantly alleviate tumor hypoxia, promote radiation-induced DNA damage, and ultimately inhibit tumor growth in vivo. The miR181a-2-3p (miR181a) serum levels in patients are predictive of the response to preoperative radiotherapy in locally advanced esophageal squamous cell carcinoma (ESCC) and facilitate personalized treatment. Moreover, miR181a can act as a radiosensitizer by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, the GDY-CeO nanocomposites with miR181a are conjugated with the iRGD-grafted polyoxyethylene glycol (short for nano-miR181a), which can increase the stability, efficiently deliver miR181a to tumor, and exhibit low toxicity. Notably, nano-miR181a can overcome radioresistance and enhance therapeutic efficacy both in a subcutaneous tumor model and human-patient-derived xenograft models. Overall, this GDY-CeO nanozyme and miR181a-based multisensitized radiotherapy strategy provides a promising therapeutic approach for ESCC.
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http://dx.doi.org/10.1002/adma.202100556DOI Listing
June 2021

Perturbation of gut microbiota plays an important role in micro/nanoplastics-induced gut barrier dysfunction.

Nanoscale 2021 May;13(19):8806-8816

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience & Technology of China, Beijing, 100190, China and College of Materials Sciences and Opto-Electronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China.

The widespread occurrence of microplastics (MPLs) and nanoplastics (NPLs), collectively abbreviated as M/NPLs, has markedly affected the ecosystem and has become a global threat to human health. Multiple investigations have shown that the chronic ingestion of M/NPLs negatively affects gut barrier function but the mechanism remains unclear. Herein, this research has investigated the toxic effects of pristine polystyrene (PS) M/NPLs, negatively charged carboxylated polystyrene M/NPLs (PS-COOH) and positively charged aminated polystyrene M/NPLs (PS-NH2) of two sizes (70 nm and 5 μm in diameter) in mice. Gavage of these PS M/NPLs for 28 days caused obvious injuries to the gut tract, leading to the decreased expression of tight junction proteins. The toxicity of the M/NPLs was ranked as PS-NH2 > PS-COOH > pristine PS. Oral administration of these M/NPLs resulted in marked gut microbiota dysbiosis. The M/NPLs-enriched genera generally contained opportunistic pathogens which are accompanied by a deteriorated intestinal barrier function, while most M/NPLs-decreased bacteria were beneficial microbes with known tight junction-promoting functions, implicating an important indirect toxic effect of gut microbiota dysbiosis in M/NPLs-induced gut barrier dysfunction. In conclusion, this research highlights the importance of gut microbiota in the toxicity of M/NPLs exposure on gut barrier function, providing novel insights into the adverse effects of M/NPLs exposure on human health.
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http://dx.doi.org/10.1039/d1nr00038aDOI Listing
May 2021

Inherited and acquired corona of coronavirus in the host: Inspiration from the biomolecular corona of nanoparticles.

Nano Today 2021 Aug 17;39:101161. Epub 2021 Apr 17.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

The family of coronavirus are named for their crown shape. Encoded by the genetic material inherited from the coronavirus itself, this intrinsic well-known "viral corona" is considered an "inherited corona". After contact with mucosa or the entrance into the host, bare coronaviruses can become covered by a group of dissolved biomolecules to form one or multiple layers of biomolecules. The layers acquired from the surrounding environment are named the "acquired corona". We highlight here the possible role of the acquired corona in the pathogenesis of coronaviruses, which will generate fresh insight into the nature of various coronavirus-host interactions.
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http://dx.doi.org/10.1016/j.nantod.2021.101161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052473PMC
August 2021

Design and application of nanoparticles as vaccine adjuvants against human corona virus infection.

J Inorg Biochem 2021 06 29;219:111454. Epub 2021 Mar 29.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China; GBA National Institute for Nanotechnology Innovation, Guangdong 510700, PR China; Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100021, PR China. Electronic address:

In recent years, some viruses have caused a grave crisis to global public health, especially the human coronavirus. A truly effective vaccine is therefore urgently needed. Vaccines should generally have two features: delivering antigens and modulating immunity. Adjuvants have an unshakable position in the battle against the virus. In addition to the perennial use of aluminium adjuvant, nanoparticles have become the developing adjuvant candidates due to their unique properties. Here we introduce several typical nanoparticles and their antivirus vaccine adjuvant applications. Finally, for the combating of the coronavirus, we propose several design points, hoping to provide ideas for the development of personalized vaccines and adjuvants and accelerate the clinical application of adjuvants.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007196PMC
June 2021

Comparative nanometallomics as a new tool for nanosafety evaluation.

Metallomics 2021 04;13(4)

University of Chinese Academy of Sciences, Beijing 100049, China.

Nanosafety evaluation is paramount since it is necessary not only for human health protection and environmental integrity but also as a cornerstone for industrial and regulatory bodies. The current nanometallomics did not cover non-metallic nanomaterials, which is an important part of nanomaterials. In this critical review, the concept of nanometallomics was expanded to incorporate all nanomaterials. The impacts on metal(loid) and metallo-biomolecular homeostasis by nanomaterials will be focused upon in nanometallomics study. Besides, the impacts on elemental and biomolecular homeostasis by metallo-nanomaterials are also considered as the research subjects of nanometallomics. Based on the new concept of nanometallomics, comparative nanometallomics was proposed as a new tool for nanosafety evaluation, which is high throughput and will be precise considering the nature of machine learning techniques. The perspectives of nanometallomics like metallo-wide association study and non-target nanometallomics were put forward.
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http://dx.doi.org/10.1093/mtomcs/mfab013DOI Listing
April 2021

Postchronic Single-Walled Carbon Nanotube Exposure Causes Irreversible Malignant Transformation of Human Bronchial Epithelial Cells through DNA Methylation Changes.

ACS Nano 2021 04 24;15(4):7094-7104. Epub 2021 Mar 24.

Department of Toxicology, School of Public Health, Medicine College, Soochow University, Suzhou 215123, China.

As environmental pollutants and possible carcinogens, carbon nanotubes (CNTs) have recently been found to induce carcinogenesis and tumor metastasis after long-term pulmonary exposure. However, whether CNT-induced carcinogenesis can be inherited and last for generations remains unclear. Herein, postchronic single-walled carbon nanotubes (SWCNTs) exposed human lung cell model (BEAS-2B cells) are established to investigate SWCNT-induced carcinogenesis. At a tolerated sublethal dose level, postchronic SWCNT exposure significantly increases the migration and invasion abilities of BEAS-2B cells, leading to malignant cell transformation. Notably, the malignant transformation of BEAS-2B cells is irreversible within a 60 day recovery period after SWCNT exposure, and the malignant transformation activities of cells gradually increase during the recovery period. Moreover, these transformed cells promote carcinogenesis , accompanied by a raised level of biomarkers of lung adenocarcinoma. Further mechanism analyses reveal that postchronic exposure to SWCNTs causes substantial DNA methylation and transcriptome dysregulation of BEAS-2B cells. Subsequent enrichment and clinical database analyses reveal that differentially expressed/methylated genes of BEAS-2B cells are enriched in cancer-related biological pathways. These results not only demonstrate that postchronic SWCNT-exposure-induced carcinogenesis is heritable but also uncover a mechanism from the perspective of DNA methylation.
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http://dx.doi.org/10.1021/acsnano.1c00239DOI Listing
April 2021

Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus.

Nano Today 2021 Jun 19;38:101139. Epub 2021 Mar 19.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences (CAS), Beijing 100190, China.

Effective vaccines are vital to fight against the COVID-19 global pandemic. As a critical component of a subunit vaccine, the adjuvant is responsible for strengthening the antigen-induced immune responses. Here, we present a new nanovaccine that comprising the Receptor-Binding Domain (RBD) of spike protein and the manganese nanoadjuvant (MnARK), which induces humoral and cellular responses. Notably, even at a 5-fold lower antigen dose and with fewer injections, the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (~270-fold) and live coronavirus (>8-fold) than that of Alum-adsorbed RBD vaccine (Alu-RBD). Furthermore, we found that the effective co-delivery of RBD antigen and MnARK to lymph nodes (LNs) elicited an increased cellular internalization and the activation of immune cells, including DCs, CD4 and CD8 T lymphocytes. Our findings highlight the importance of MnARK adjuvant in the design of novel coronavirus vaccines and provide a rationale strategy to design protective vaccines through promoting cellular internalization and the activation of immune-related pathways.
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http://dx.doi.org/10.1016/j.nantod.2021.101139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972805PMC
June 2021

X-ray-Based Techniques to Study the Nano-Bio Interface.

ACS Nano 2021 03 2;15(3):3754-3807. Epub 2021 Mar 2.

Mathematics, Informatics, and Natural Sciences (MIN) Faculty, University of Hamburg, 20354 Hamburg, Germany.

X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologies (including those performed at synchrotron light sources and X-ray free-electron lasers) and their potentials for application to investigate the nano-bio interface. The discussion is predominantly guided by asking how such methods could better help to understand and to improve nanoparticle-based drug delivery, though the concepts also apply to nano-bio interactions in general. We discuss current limitations and how they might be overcome, particularly for future use .
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http://dx.doi.org/10.1021/acsnano.0c09563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992135PMC
March 2021

Molybdenum derived from nanomaterials incorporates into molybdenum enzymes and affects their activities in vivo.

Nat Nanotechnol 2021 06 18;16(6):708-716. Epub 2021 Feb 18.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China.

Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport-transformation-bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism.
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http://dx.doi.org/10.1038/s41565-021-00856-wDOI Listing
June 2021

Towards screening the neurotoxicity of chemicals through feces after exposure to methylmercury or inorganic mercury in rats: A combined study using gut microbiome, metabolomics and metallomics.

J Hazard Mater 2021 05 30;409:124923. Epub 2020 Dec 30.

CAS-HKU Joint Laboratory of Metallomics on Health and Environment, & CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & Beijing Metallomics Facility, & National Consortium for Excellence in Metallomics, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Mercury (Hg) is one of the chemicals that bring serious adverse effects to the environment and human beings. Methylmercury (MeHg) is a neurotoxin while inorganic Hg (IHg) is not. Early screening of the neurotoxicity of chemicals may help reduce the occurrence of neurological disorders by minimizing chemical exposure. This work proposed the combined application of gut microbiome, metabolomics and metallomics to differentiate the neurotoxicity between MeHg and IHg in rats. It was found that MeHg caused down-regulated Bacteroides, Firmicutes and Proteobacteria, and up-regulated Actinobacteria and Verrucomicrobia at phylum level, while MeHg caused up-regulated Verrucomicrobiaceae, Desulfovibrionaceae, Helicobacteraceae, Lachnospiraceae and down-regulated Rikenellaceae, Erysipelotrichaceae, Sutterellaceae, Anaeroplasmataceae and Coriobacteriaceae in feces than IHg did at family level; Besides, MeHg brought metabolites change in activation of gut-brain axis pathway than IHg did, such as Glutamate, γ-aminobutyric acid (GABA), Dopamine (DA) and Tryptophan. These differences between MeHg and IHg were further confirmed by the distribution of Hg in the intestine, as well as the level of brain-derived neurotrophic factor (BDNF) in the intestine, brain and serum. Therefore, the difference of toxicity between MeHg and IHg can be well distinguished through feces after exposure for only 24 h, which may be used for the screening of neurotoxicity of other chemicals.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124923DOI Listing
May 2021

Assessment of Air Pollutant PM2.5 Pulmonary Exposure Using a 3D Lung-on-Chip Model.

ACS Biomater Sci Eng 2020 05 7;6(5):3081-3090. Epub 2020 Apr 7.

Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China 116023.

Airborne particulate matters have posed significant risk to human health worldwide. Fine particulate matters (PM2.5, aerodynamic diameter <2.5 μm) are associated with increased morbidity and mortality attributed to pulmonary diseases. An advanced model would benefit the assessment of PM2.5 induced pulmonary injuries and drug development. In this work, we present a PM2.5 exposure model to evaluate the pulmonary risk of fine particulate matter exposure in an organotypic manner with the help of 3D human lung-on-a-chip. By compartmentalized co-culturing of human endothelial cells, epithelial cells, and extra cellular matrix, our lung-on-a-chip recapitulated the structural features of the alveolar-blood barrier, which is pivotal for exogenous hazard toxicity evaluation. PM2.5 was applied to the channel lined with lung epithelial cells to model the pulmonary exposure of fine particulate matter. The results indicated acute high dose PM2.5 exposure would lead to various malfunctions of the alveolar-capillary barrier, including adheren junction disruption, increased ROS generation, apoptosis, inflammatory biofactor expression in epithelial cells and endothelial cells, elevated permeability, and monocyte attachments. Collectively, our lung-on-a-chip model provides a simple platform to investigate the complex responses after PM2.5 exposure in a physiologically relevant level, which could be of great potential in environmental risk assessment and therapeutic treatment development.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00221DOI Listing
May 2020

Time-course effect of ultrasmall superparamagnetic iron oxide nanoparticles on intracellular iron metabolism and ferroptosis activation.

Nanotoxicology 2021 04 16;15(3):366-379. Epub 2021 Jan 16.

School of Public Health, Qingdao University, Qingdao, China.

Ferroptosis is an iron-dependent cell death caused by excessive peroxidation of polyunsaturated fatty acids. It can be activated by iron-based nanoparticles as a potential cancer therapeutic target. However, the intracellular transformation of iron-based nanoparticles is still ambiguous and the subsequent ferroptosis mechanism is also obscure. Here, we identified the time-course metabolism of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) in cells by using X-ray absorption near edge structure spectroscopy. Also, the integrated quantitative transcriptome and proteome data obtained from the cells exposed to USPIO exhibited hallmark features of ferroptosis. With the chemical species of iron oxide transforming to ferritin, the intracellular GPX4 down-regulated, and lipid peroxide began to accumulate. These results provide evidence that the intracellular metabolism of USPIO induced ferroptosis in a time-dependent manner, and iron over-loaded in cytoplasm along with lipid peroxidation of the membrane are involved in the detailed mechanism of ferroptosis signaling activation.
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http://dx.doi.org/10.1080/17435390.2021.1872112DOI Listing
April 2021

Hypoxia-Triggered Self-Assembly of Ultrasmall Iron Oxide Nanoparticles to Amplify the Imaging Signal of a Tumor.

J Am Chem Soc 2021 02 4;143(4):1846-1853. Epub 2021 Jan 4.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, People's Republic of China.

Hypoxia is a common phenomenon among most solid tumors that significantly influences tumor response toward chemo- and radiotherapy. Understanding the distribution and extent of tumor hypoxia in patients will be very important to provide personalized therapies in the clinic. Without sufficient vessels, however, traditional contrast agents for clinical imaging techniques will have difficulty in accumulating in the hypoxic region of solid tumors, thus challenging the detection of hypoxia To overcome this problem, herein we develop a novel hypoxia imaging probe, consisting of a hypoxia-triggered self-assembling ultrasmall iron oxide (UIO) nanoparticle and assembly-responding fluorescence dyes (NBD), to provide dual-mode imaging . In this strategy, we have employed nitroimidazole derivatives as the hypoxia-sensitive moiety to construct intermolecular cross-linking of UIO nanoparticles under hypoxia, which irreversibly form larger nanoparticle assemblies. The hypoxia-triggered performance of UIO self-assembly not only amplifies its -weighted MRI signal but also promotes the fluorescence intensity of NBD through its emerging hydrophobic environment incorporated into self-assemblies. results further confirm that our hypoxic imaging probe can display a prompt MRI signal for the tumor interior region, and its signal enhancement performs a long-term effective feature and gradually reaches 3.69 times amplification. Simultaneously, this probe also exhibits obvious green fluorescence in the hypoxic region of tumor sections. Accordingly, we also have developed a MRI difference value method to visualize the 3D distribution and describe the extent of the hypoxic tumor region within the whole bodies of mice. Due to its notable efficiency of penetration and accumulation inside a hypoxic tumor, our hypoxia imaging probe could also be considered as a potential candidate as a versatile platform for hypoxia-targeted drug delivery, and meanwhile its hypoxia-related therapeutic efficacy can be monitored.
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http://dx.doi.org/10.1021/jacs.0c10245DOI Listing
February 2021

3D Imaging and Quantification of the Integrin at a Single-Cell Base on a Multisignal Nanoprobe and Synchrotron Radiation Soft X-ray Tomography Microscopy.

Anal Chem 2021 01 30;93(3):1237-1241. Epub 2020 Dec 30.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100090, China.

The development of three-dimensional (3D) single-cell imaging and protein quantitative methods can provide more comprehensive information for diagnoses. We report the design and synthesis of a multisignal nanoprobe ([email protected]) for single-cell 3D imaging and quantifying the integrin αβ using correlated synchrotron radiation soft X-ray tomography microscopy and an iterative tomographic algorithm termed equally sloped tomography for the first time. Moreover, on the basis of the Au or Gd content of our nanoprobe, the number of integrin αβ on a single cell also can be accurately quantified (1.5 × 10 per cell) via inductively coupled plasma mass spectrometry.
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http://dx.doi.org/10.1021/acs.analchem.0c04662DOI Listing
January 2021

percutaneous permeation of gold nanomaterials in consumer cosmetics: implication in dermal safety assessment of consumer nanoproducts.

Nanotoxicology 2021 02 28;15(1):131-144. Epub 2020 Dec 28.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, P. R. China.

The increasing emergence of nano-cosmetics in the marketplace provokes safety concerns with respect to percutaneous permeation and toxicity of nanomaterials inside the human body. In this study, percutaneous permeation and dermal safety of cosmetic cream containing Au nanosheets and extracted Au nanosheets from cosmetic creams are investigated with guinea pigs. Quantitative percutaneous permeation data suggests that Au nanosheets in cosmetic creams permeate into the skin epidermis, dermis, and subcutaneous layer after 10 d cutaneous exposure, but cannot enter the systemic circulation. However, more Au nanosheets are accumulated in the skin and the permeation of Au nanosheets increased after embedded into the cream matrix. Synchrotron radiation X-ray fluorescence (SRXRF) imaging reveals that Au nanosheets in cosmetics penetrate mainly through hair follicles in a time-dependent manner. Cosmetic creams rather than extracted Au nanosheets decrease the cell viability of keratinocytes and slightly induce apoptosis/necrosis of keratinocytes and skin dermal fibroblasts. Intriguingly, the growth of hair is inhibited by the cosmetic cream and the extracted Au nanosheets revealed by HE staining and immunohistochemistry (IHC) assay. Altogether this study provides insights into the comprehensive understanding of percutaneous permeation and dermal safety of cosmetic creams containing Au nanosheets. This work provides reliable methods to study the skin permeation, biodistribution, and dermal safety of nano-cosmetics and reminds the community of the crucial need to combine the assays at molecular, cellular, and organ levels in nanotoxicology research.
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http://dx.doi.org/10.1080/17435390.2020.1860264DOI Listing
February 2021

Tumor-Associated Macrophage and Tumor-Cell Dually Transfecting Polyplexes for Efficient Interleukin-12 Cancer Gene Therapy.

Adv Mater 2021 Jan 3;33(2):e2006189. Epub 2020 Dec 3.

Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, P. R. China.

Interleukin 12 (IL12) is a potent pro-inflammatory chemokine with multifunction, including promoting cytotoxic T-cell-mediated killing of cancer cells. IL12-based cancer gene therapy can overcome IL12's life-threatening adverse effects, but its clinical translation has been limited by the lack of systemic gene-delivery vectors capable of efficiently transfecting tumors to produce sufficient local IL12. Macrophages inherently excrete IL12, and tumor-associated macrophages (TAMs) are the major tumor component taking up a large fraction of the vectors arriving in the tumor. It is thus hypothesized that a gene vector efficiently transfecting both cancer cells and TAMs would make the tumor to produce sufficient IL12; however, gene transfection of TAMs is challenging due to their inherent strong degradation ability. Herein, an IL12 gene-delivery vector is designed that efficiently transfects both cancer cells and TAMs to make them as a factory for IL12 production, which efficiently activates anticancer immune responses and remodels the tumor microenvironment, for instance, increasing the M1/M2 ratio by more than fourfold. Therefore, the intravenously administered vector retards tumor growth and doubles survival in three animal models' with negligible systemic toxicities. This work reports the first nonviral IL12 gene delivery system that effectively makes use of both macrophages and tumor cells.
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http://dx.doi.org/10.1002/adma.202006189DOI Listing
January 2021

Using nano-selenium to combat Coronavirus Disease 2019 (COVID-19)?

Nano Today 2021 Feb 23;36:101037. Epub 2020 Nov 23.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, & CAS-HKU Joint Laboratory of Metallomics on Health and Environment, & Beijing Metallomics Facility, & National Consortium for Excellence in Metallomics, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

The coronavirus disease 2019 (COVID-19) pandemic represents a severe global health threat. Selenium (Se), as one of the essential trace elements in human body, is well known for its antioxidant and immunity-boosting capabilities that induce a strong antiviral effect. In response to the global pandemic, we highlight here the current status of Se in combating different viruses, as well as the potential application of nano-selenium (nanoSe) in combating COVID-19.
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http://dx.doi.org/10.1016/j.nantod.2020.101037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683300PMC
February 2021

Few-Layer Bismuthene for Checkpoint Knockdown Enhanced Cancer Immunotherapy with Rapid Clearance and Sequentially Triggered One-for-All Strategy.

ACS Nano 2020 11 6;14(11):15700-15713. Epub 2020 Nov 6.

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, University of Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

As a conceptually attractive strategy, the use of immune checkpoint blockade antibodies to treat cancer is limited due to the restrained tumor-infiltrating lymphocytes (TILs), poor accumulation and penetration of antibodies, and deficient checkpoint blockade in malignancies. In this study, we describe a pH and mild photothermal sequentially triggered PD-L1 siRNA release nanosystem, based on monoelemental bismuthene, as a one-for-all strategy to realize enhanced tumor mild photothermal immunotherapy. Under manually controlled NIR irradiation, the bismuthene-based nanosystem simultaneously induces a tumor-enhanced pathological permeability and retention (EPPR) effect, increases TIL recruitment, and triggers programmed siRNA release, thereby amplifying anti-PD-L1 immunotherapy. In addition, the nanosystem's rapid removal through intestinal and renal clearance mitigates toxicity risk associated with long-term retention. antitumor experiments demonstrate that this bismuthene-based nanosystem is a promising and effective approach for "cold" tumor management.
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http://dx.doi.org/10.1021/acsnano.0c06656DOI Listing
November 2020

Letter on a Prospective Study of the Efficacy of Cell-Assisted Lipotransfer with Stromal Vascular Fraction to Correct Contour Deformities of the Autologous Reconstructed Breast.

Aesthetic Plast Surg 2021 06 3;45(3):1359. Epub 2020 Nov 3.

Central South Hospital of Wuhan University, No.169 Donghu Road Wuchang District, Wuhan City, Hubei Province, People's Republic of China.

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http://dx.doi.org/10.1007/s00266-020-02020-6DOI Listing
June 2021

Implications of the Human Gut-Brain and Gut-Cancer Axes for Future Nanomedicine.

ACS Nano 2020 11 2;14(11):14391-14416. Epub 2020 Nov 2.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.

Recent clinical and pathological evidence have implicated the gut microbiota as a nexus for modulating the homeostasis of the human body, impacting conditions from cancer and dementia to obesity and social behavior. The connections between microbiota and human diseases offer numerous opportunities in medicine, most of which have limited or no therapeutic solutions available. In light of this paradigm-setting trend in science, this review aims to provide a comprehensive and timely summary of the mechanistic pathways governing the gut microbiota and their implications for nanomedicines targeting cancer and neurodegenerative diseases. Specifically, we discuss in parallel the beneficial and pathogenic relationship of the gut microbiota along the gut-brain and gut-cancer axes, elaborate on the impact of dysbiosis and the gastrointestinal corona on the efficacy of nanomedicines, and highlight a molecular mimicry that manipulates the universal cross-β backbone of bacterial amyloid to accelerate neurological disorders. This review further offers a forward-looking section on the rational design of cancer and dementia nanomedicines exploiting the gut-brain and gut-cancer axes.
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http://dx.doi.org/10.1021/acsnano.0c07258DOI Listing
November 2020
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