Publications by authors named "Shaoli Liu"

39 Publications

Theoretical study on water behavior on the copper surfaces.

J Mol Model 2021 May 3;27(5):149. Epub 2021 May 3.

College of Chemistry and Chemical Engineering, Yantai University, Yantai, 264005, People's Republic of China.

We calculated the adsorption of H, O, OH, and HO and the dissociation of HO molecule on the Cu(111), Cu(100), and Cu(110) surfaces using density functional theory. H, O, and OH tend to adsorb stably at the highly coordinated dh and h sites on the Cu(111) and Cu(100) surfaces. OH and H tend to adsorb on sb site on the Cu(110) surface. The more charge transfer of the adsorbed substance, the more stable the adsorption. The dissociation product is O+H on the Cu(111) surface, while the dissociation product is OH+H on the Cu(100) and Cu(110) surfaces. Due to the different geometric structures of initial state (IS), transition state (TS), and final state (FS) in the dissociation reaction, the dissociation of water on the copper surface does not establish a linear Brønsted-Evans-Polanyi (BEP) relationship. These results provide theoretical support for the understanding of the interaction between water and metals as well as the behavior of water molecules.
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http://dx.doi.org/10.1007/s00894-021-04751-yDOI Listing
May 2021

A Nucleic Acid/Gold Nanorod-Based Nanoplatform for Targeted Gene Editing and Combined Tumor Therapy.

ACS Appl Mater Interfaces 2021 May 28;13(18):20974-20981. Epub 2021 Apr 28.

School of Materials Science and Engineering, Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, China.

The CRISPR/Cas9 gene-editing system has become a promising strategy for tumor therapy with its powerful oncogene-editing ability. However, the efficient delivery of sgRNA/Cas9 complex into target tumor cells remains a challenge. Herein, we report a facile strategy for the construction of an sgRNA/Cas9 complex co-assembled nanoplatform for targeted gene editing and combined tumor therapy. In our design, the TAT peptide and thiolated DNA linker functionalized gold nanorod can efficiently load the sgRNA/Cas9 complex through the hybridization between the 3' overhang of sgRNA and the DNA linker. Due to the integration of an active cell targeting group (aptamer) and nuclear targeting peptide (TAT), the multifunctional nanoplatform can elicit the targeted cellular internalization and efficient nuclear targeting transportation to realize endogenous RNase H activated gene editing of the tumor-associated gene polo-like kinase 1 (PLK1). With mild photothermal treatment, this sgRNA/Cas9 complex loaded nanoplatform achieved efficient inhibition of tumor cell proliferation. This multifunctional nanocarrier provides a new strategy for the development of combined tumor therapy.
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http://dx.doi.org/10.1021/acsami.1c02122DOI Listing
May 2021

A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis.

Nat Commun 2021 01 13;12(1):358. Epub 2021 Jan 13.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 100190, Beijing, China.

Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.
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http://dx.doi.org/10.1038/s41467-020-20638-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807036PMC
January 2021

Theoretical study on water adsorption and dissociation on the nickel surfaces.

J Mol Model 2021 Jan 9;27(2):36. Epub 2021 Jan 9.

College of Chemistry and Chemical Engineering, Yantai University, Yantai, 264005, People's Republic of China.

Using density functional theory methods, HO dissociation was investigated on the Ni(111), Ni(100), and Ni(110) surfaces. H and O atom as well as OH species adsorb stably at the high coordination sites. While on the Ni(110) surface, the OH species prefers at the twofold short bridge site because the adsorption on the fourfold hollow site is less feasible due to the increased distances between the nickel atoms. The amount of charge transfer is related to the adsorption stability. The more charge transfer, the more stable the adsorption. The charge transfer decreases in the order of O > OH > H. HO molecule adsorbs at the top site in a configuration parallel to the surface. The final products are different for HO dissociation due to the different mechanisms. On the Ni(111) surface, the final product is the O atom. On the Ni(100) and Ni(110) surfaces, the most abundant species are OH and H, but the reaction mechanisms were different. It is not necessary to linear BEP relationship for a given reaction on different surfaces. These results could provide fundamental insights into water behaviors and a favorable theoretical basis for further understanding and research on the interaction between water and metal surfaces.
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http://dx.doi.org/10.1007/s00894-020-04662-4DOI Listing
January 2021

A Tubular DNA Nanodevice as a siRNA/Chemo-Drug Co-delivery Vehicle for Combined Cancer Therapy.

Angew Chem Int Ed Engl 2021 02 1;60(5):2594-2598. Epub 2020 Dec 1.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 11 BeiYiTiao, ZhongGuanCun, Beijing, 100190, China.

Using the DNA origami technique, we constructed a DNA nanodevice functionalized with small interfering RNA (siRNA) within its inner cavity and the chemotherapeutic drug doxorubicin (DOX), intercalated in the DNA duplexes. The incorporation of disulfide bonds allows the triggered mechanical opening and release of siRNA in response to intracellular glutathione (GSH) in tumors to knockdown genes key to cancer progression. Combining RNA interference and chemotherapy, the nanodevice induced potent cytotoxicity and tumor growth inhibition, without observable systematic toxicity. Given its autonomous behavior, exceptional designability, potent antitumor activity and marked biocompatibility, this DNA nanodevice represents a promising strategy for precise drug design for cancer therapy.
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http://dx.doi.org/10.1002/anie.202009842DOI Listing
February 2021

Publisher Correction: A DNA nanodevice-based vaccine for cancer immunotherapy.

Nat Mater 2021 Mar;20(3):431-433

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China.

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http://dx.doi.org/10.1038/s41563-020-00824-0DOI Listing
March 2021

A DNA nanodevice-based vaccine for cancer immunotherapy.

Nat Mater 2021 03 7;20(3):421-430. Epub 2020 Sep 7.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China.

A major challenge in cancer vaccine therapy is the efficient delivery of antigens and adjuvants to stimulate a controlled yet robust tumour-specific T-cell response. Here, we describe a structurally well defined DNA nanodevice vaccine generated by precisely assembling two types of molecular adjuvants and an antigen peptide within the inner cavity of a tubular DNA nanostructure that can be activated in the subcellular environment to trigger T-cell activation and cancer cytotoxicity. The integration of low pH-responsive DNA 'locking strands' outside the nanostructures enables the opening of the vaccine in lysosomes in antigen-presenting cells, exposing adjuvants and antigens to activate a strong immune response. The DNA nanodevice vaccine elicited a potent antigen-specific T-cell response, with subsequent tumour regression in mouse cancer models. Nanodevice vaccination generated long-term T-cell responses that potently protected the mice against tumour rechallenge.
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http://dx.doi.org/10.1038/s41563-020-0793-6DOI Listing
March 2021

Effect of potassium on carbon adsorption on the Co(0001) surface.

J Mol Model 2020 May 12;26(6):134. Epub 2020 May 12.

College of Chemistry and Chemical Engineering, Yantai University, Yantai, 264005, People's Republic of China.

The effect of potassium on carbon adsorption and deposition on the Co(0001) surface was studied on the basis of theoretical calculations. Thermodynamically, the surface C species is expected, and C dimer may be a critical elementary unit. With the increase of carbon coverage, a fraction of the carbon atoms may diffuse into the subsurface. But kinetically, the formation of C species is more favorable, and there is no driving force for carbon to migrate into the subsurface. As the surface carbon concentration increases, the adsorbed carbon atoms turn into carbon chains and then into graphene sheets parallel to the surface. Potassium promoter has little effect on the most stable adsorption configurations of carbon atoms but increases the adsorption energy of carbon species, which can be explained by the decreasing of the surface work function resulting from the electron effect of potassium promoter. The potassium promotes carbon deposition and carbonization of the cobalt surface to a certain extent. These results could support some useful information for the carbon deposition and cobalt carbide formation.
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http://dx.doi.org/10.1007/s00894-020-04390-9DOI Listing
May 2020

Cold-Stress Response of Probiotic K25 by iTRAQ Proteomic Analysis.

J Microbiol Biotechnol 2020 Feb;30(2):187-195

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University Beijing, P.R. China.

To understand the molecular mechanism involved in the survivability of cold-tolerant lactic acid bacteria was of great significance in food processing, since these bacteria play a key role in a variety of low-temperature fermented foods. In this study, the cold-stress response of probiotic K25 isolated from Tibetan kefir grains was analyzed by iTRAQ proteomic method. By comparing differentially expressed (DE) protein profiles of the strain incubated at 10°C and 37°C, 506 DE proteins were identified. The DE proteins involved in carbohydrate, amino acid and fatty acid biosynthesis and metabolism were significantly down-regulated, leading to a specific energy conservation survival mode. The DE proteins related to DNA repair, transcription and translation were up-regulated, implicating change of gene expression and more protein biosynthesis needed in response to cold stress. In addition, two-component system, quorum sensing and ABC (ATP-binding cassette) transporters also participated in cell cold-adaptation process. These findings provide novel insight into the cold-resistance mechanism in with potential application in low temperature fermented or preserved foods.
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http://dx.doi.org/10.4014/jmb.1909.09021DOI Listing
February 2020

A Self-Assembled Platform Based on Branched DNA for sgRNA/Cas9/Antisense Delivery.

J Am Chem Soc 2019 12 20;141(48):19032-19037. Epub 2019 Nov 20.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China.

Precisely assembled DNA nanostructures are promising candidates for the delivery of biomolecule-based therapeutics. Herein, we introduce a facile strategy for the construction of a branched DNA-based nanoplatform for codelivery of gene editing (sgRNA/Cas9, targeting DNA in the nucleus) and gene silencing (antisense, targeting mRNA in the cytoplasm) components for synergistic tumor therapy in vitro and in vivo. In our design, the branched DNA structure can efficiently load a sgRNA/Cas9/antisense complex targeting a tumor-associated gene, PLK1, through DNA self-assembly. With the incorporation of an active targeting aptamer and an endosomal escape peptide by host-guest interaction, the biocompatible DNA nanoplatform demonstrates efficient inhibition of tumor growth without apparent systemic toxicity. This multifunctional DNA nanocarrier provides a new strategy for the development of gene therapeutics.
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http://dx.doi.org/10.1021/jacs.9b09043DOI Listing
December 2019

Evaluation and Proteomic Analysis of Lead Adsorption by Lactic Acid Bacteria.

Int J Mol Sci 2019 Nov 6;20(22). Epub 2019 Nov 6.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China.

Heavy metals are a growing threat to human health due to the resulting damage to the ecology; the removal of heavy metals by lactic acid bacteria (LAB) has been a focus of many studies. In this study, 10 LAB strains were evaluated for their ability to absorb and tolerate lead. Lactobacillus plantarum YW11 was found to possess the strongest ability of lead absorbing and tolerance, with the rate of absorption as high as 99.9% and the minimum inhibitory concentration of lead on YW11 higher than 1000 mg/L. Based on the isobaric tags for relative and absolute quantitation (iTRAQ) proteomics analysis of YW11, a total of 2009 proteins were identified both in the lead-treated strain and the control without the lead treatment. Among these proteins, 44 different proteins were identified. The abundance of 25 proteins increased significantly, and 19 proteins decreased significantly in the treatment group. These significantly differential abundant proteins are involved in the biological processes of amino acid and lipid metabolism, energy metabolism, cell wall biosynthesis, and substance transport. This study contributed further understanding of the molecular mechanism of L. plantarum in the binding and removal of lead to explore its potential application in counteracting heavy metal pollution of environment, food, and other fields.
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http://dx.doi.org/10.3390/ijms20225540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888269PMC
November 2019

A Nanobody-Conjugated DNA Nanoplatform for Targeted Platinum-Drug Delivery.

Angew Chem Int Ed Engl 2019 10 27;58(40):14224-14228. Epub 2019 Aug 27.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 11 BeiYiTiao, ZhongGuanCun, Beijing, 100190, China.

The targeted delivery of chemotherapeutic drugs is a major challenge in the clinical treatment of cancer. Herein, we constructed a multifunctional DNA nanoplatform as a versatile carrier of the highly potent platinum-based DNA intercalator, 56MESS. In our rational design, 56MESS was efficiently loaded into the double-bundle DNA tetrahedron through intercalation with the DNA duplex. With the integration of a nanobody that both targets and blocks epidermal growth factor receptor (EGFR), the DNA nanocarriers exhibit excellent selectivity for cells with elevated EGFR expression (a common biomarker related to tumor formation) and combined tumor therapy without obvious systemic toxicity. This DNA-based platinum-drug delivery system provides a promising strategy for the treatment of tumors.
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http://dx.doi.org/10.1002/anie.201909345DOI Listing
October 2019

Tumor-Specific Silencing of Tissue Factor Suppresses Metastasis and Prevents Cancer-Associated Hypercoagulability.

Nano Lett 2019 07 10;19(7):4721-4730. Epub 2019 Jun 10.

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

Within tumors, the coagulation-inducing protein tissue factor (TF), a major initiator of blood coagulation, has been shown to play a critical role in the hematogenous metastasis of tumors, due to its effects on tumor hypercoagulability and on the mediation of interactions between platelets and tumor cells. Targeting tumor-associated TF has therefore great therapeutic potential for antimetastasis therapy and preventing thrombotic complication in cancer patients. Herein, we reported a novel peptide-based nanoparticle that targets delivery and release of small interfering RNA (siRNA) into the tumor site to silence the expression of tumor-associated TF. We showed that suppression of TF expression in tumor cells blocks platelet adhesion surrounding tumor cells . The downregulation of TF expression in intravenously administered tumor cells (i.e., simulated circulating tumor cells [CTCs]) prevented platelet adhesion around CTCs and decreased CTCs survival in the lung. In a breast cancer mouse model, siRNA-containing nanoparticles efficiently attenuated TF expression in the tumor microenvironment and remarkably reduced the amount of lung metastases in both an experimental lung metastasis model and tumor-bearing mice. What's more, this strategy reversed the hypercoagulable state of the tumor bearing mice by decreasing the generation of thrombin-antithrombin complexes (TAT) and activated platelets, both of which are downstream products of TF. Our study describes a promising approach to combat metastasis and prevent cancer-associated thrombosis, which advances TF as a therapeutic target toward clinic applications.
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http://dx.doi.org/10.1021/acs.nanolett.9b01785DOI Listing
July 2019

Biomedical Applications of DNA-Based Molecular Devices.

Adv Healthc Mater 2019 05 2;8(10):e1801658. Epub 2019 Apr 2.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing, 100190, China.

Strict Watson-Crick base pairing and availability by automated synthesis have allowed deoxyribonucleic acid (DNA) molecules to be used as engineerable building blocks for constructing versatile nanostructures. In recent decades, with the development of DNA nanotechnology, a range of DNA-based dynamic molecular devices with sophisticated nanostructures have been designed and constructed. Featuring programmability and biocompatibility, the applications of DNA-based nanodevices have been extensively focused on the interfaces of biological systems. This review summarizes the recent progress in the design of DNA devices exhibiting programmable functions for biomedical applications. In vitro and in vivo applications of DNA-based nanodevices in cellular imaging and systemic drug delivery are highlighted. The challenges and open opportunities are also discussed.
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http://dx.doi.org/10.1002/adhm.201801658DOI Listing
May 2019

Efficient Intracellular Delivery of RNase A Using DNA Origami Carriers.

ACS Appl Mater Interfaces 2019 Mar 19;11(12):11112-11118. Epub 2019 Mar 19.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience , National Center for NanoScience and Technology , 11 BeiYiTiao , ZhongGuanCun, Beijing 100190 , China.

Delivery of proteins to carry out desired biological functions is a direct approach for disease treatment. However, protein therapy is still facing challenges due to low delivery efficiency, poor targeting during trafficking, insufficient therapeutic efficacy, and possible toxicity induced by carriers. Here, we present a novel delivery platform based on DNA origami nanostructure that enables tumor cell transportation of active proteins for cancer therapy. In our design, cytotoxic protein ribonuclease (RNase) A molecules are organized on the rectangular DNA origami nanosheets, which work as nanovehicles to deliver RNase A molecules into the cytoplasm and execute their cell-killing function inside the tumor cells. Cancer cell-targeting aptamers are also integrated onto the DNA origami-based nanoplatform to enhance its targeting effect. This DNA origami-protein coassembling strategy can be further developed to transport other functional proteins and therapeutic components simultaneously for synergistic effects and be adapted for integrated diagnostics and therapeutics.
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http://dx.doi.org/10.1021/acsami.8b21724DOI Listing
March 2019

Sucrose transporters of resistant grapevine are involved in stress resistance.

Plant Mol Biol 2019 May 26;100(1-2):111-132. Epub 2019 Feb 26.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Key Message: The whole promoter regions of SUTs in Vitis were firstly isolated. SUTs are involved in the adaptation to biotic and abiotic stresses. The vulnerability of Vitis vinifera to abiotic and biotic stresses limits its yields. In contrast, Vitis amurensis displays resistance to environmental stresses, such as microbial pathogens, low temperatures, and drought. Sucrose transporters (SUTs) are important regulators for plant growth and stress tolerance; however, the role that SUTs play in stress resistance in V. amurensis is not known. Using V. amurensis Ruper. 'Zuoshan-1' and V. vinifera 'Chardonnay', we found that SUC27 was highly expressed in several vegetative organs of Zuoshan-1, SUC12 was weakly expressed or absent in most organs in both the species, and the distribution of SUC11 in source and sink organs was highest in Zuoshan-1. A search for cis-regulatory elements in the promoter sequences of SUTs revealed that they were regulated by light, environmental stresses, physiological correlation, and hormones. The SUTs in Zuoshan-1 mostly show a higher and rapid response than in Chardonnay under the induction by Plasmopara viticola infection, cold, water deficit, and dark conditions. The induction of SUTs was associated with the upregulation of key genes involved in sucrose metabolism and the biosynthesis of plant hormones. These results indicate that stress resistance in Zuoshan-1 is governed by the differential distribution and induction of SUTs by various stimuli, and the subsequent promotion of sucrose metabolism and hormone synthesis.
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http://dx.doi.org/10.1007/s11103-019-00847-5DOI Listing
May 2019

Comparison of σ-/π-Hole Tetrel Bonds between TH F/F TO and H CX (X=O, S, Se).

Chemphyschem 2019 02 5;20(4):627-635. Epub 2019 Feb 5.

Laboratory of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Yantai University, Yantai, 264005, People's Republic of China.

Several σ-hole and π-hole tetrel-bonded complexes with a base H CX (X=O, S, Se) have been studied, in which TH F (T=C-Pb) and F TO (T=C and Si) act as the σ-hole and π-hole donors, respectively. Generally, these complexes are combined with a primary tetrel bond and a weak H-bond. Only one minimum tetrel-bonded structure is found for TH F, whereas two minima tetrel-bonded complexes for some F TO. H CX is favorable to engage in the π-hole complex with F TO relative to TH F in most cases, and this preference further expands for the Si complex. Particularly, the double π-hole complex between F SiO and H CX (X=S and Se) has an interaction energy exceeding 500 kJ/mol, corresponding to a covalent-bonded complex with the huge orbital interaction and polarization energy. Both the σ-hole interaction and the π-hole interaction are weaker for the heavier chalcogen atom, while the π-hole interaction involving F TO (T=Ge, Sn, and Pb) has an opposite change. Both types of interactions are electrostatic in nature although comparable contributions from dispersion and polarization are respectively important for the weaker and stronger interactions.
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http://dx.doi.org/10.1002/cphc.201800990DOI Listing
February 2019

A Tailored DNA Nanoplatform for Synergistic RNAi-/Chemotherapy of Multidrug-Resistant Tumors.

Angew Chem Int Ed Engl 2018 11 23;57(47):15486-15490. Epub 2018 Oct 23.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 11 BeiYiTiao, ZhongGuanCun, Beijing, 100190, China.

Multidrug resistance (MDR) is a major obstacle in the clinical treatment of cancer. Herein, a facile strategy is reported to construct a versatile DNA nanostructure as a co-delivery vector of RNA interference (RNAi) and chemodrugs to combat multidrug-resistant tumor (MCF-7R) in vitro and in vivo. In the tailored nanocarrier, two linear small hairpin RNA (shRNA) transcription templates targeting MDR-associated genes (gene of P-glycoprotein, a typical drug efflux pump; and gene of survivin, a representative anti-apoptotic protein) are precisely organized in the chemodrug (doxorubicin, DOX) pre-loaded DNA origami. With the incorporation of active targeting and controlled-release elements, these multifunctional DNA nanocarriers can successfully enter the target MCF-7R cells and synergistically inhibit tumor growth without apparent systemic toxicity. This tailored DNA nanoplatform, which combines RNAi therapy and chemotherapy, provides a new strategy for the treatment of multidrug-resistant tumors.
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http://dx.doi.org/10.1002/anie.201809452DOI Listing
November 2018

Rationally Designed DNA-Origami Nanomaterials for Drug Delivery In Vivo.

Adv Mater 2019 Nov 4;31(45):e1804785. Epub 2018 Oct 4.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, Beijing, 100190, China.

The recent decades have seen a surge of new nanomaterials designed for efficient drug delivery. DNA nanotechnology has been developed to construct sophisticated 3D nanostructures and artificial molecular devices that can be operated at the nanoscale, giving rise to a variety of programmable functions and fascinating applications. In particular, DNA-origami nanostructures feature rationally designed geometries and precise spatial addressability, as well as marked biocompatibility, thus providing a promising candidate for drug delivery. Here, the recent successful efforts to employ self-assembled DNA-origami nanostructures as drug-delivery vehicles are summarized. The remaining challenges and open opportunities are also discussed.
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http://dx.doi.org/10.1002/adma.201804785DOI Listing
November 2019

Specific tissue factor delivery using a tumor-homing peptide for inducing tumor infarction.

Biochem Pharmacol 2018 10 15;156:501-510. Epub 2018 Sep 15.

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

Targeting the human blood coagulation-inducing protein tissue factor (TF) to the tumor vasculature to induce infarction and disrupt the blood vessels has proven to be an effective approach for tumor therapy. In this study, we investigated the thrombogenic activity and anti-tumor potential of a novel fusion protein (tTF-CREKA) comprising the extracellular domain of human tissue factor (truncated TF, tTF) and a tumor targeting pentapeptide, Cys-Arg-Glu-Lys-Ala (CREKA). tTF is soluble and inactive in its free state, but when it is targeted to the plasma membrane of both tumor vessel endothelial cells and stromal cells by the CREKA peptide, its native coagulation-inducing activity is restored. Systemic administration of the tTF-CREKA fusion protein into tumor-bearing mice induced tumor-selective intravascular thrombosis and reduced tumor blood perfusion, consequently inhibiting tumor growth. The development of tTF-CREKA introduces a new method for treating a wide spectrum of solid tumors by selectively blocking tumor blood supply.
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http://dx.doi.org/10.1016/j.bcp.2018.09.020DOI Listing
October 2018

Overexpression of 9--Epoxycarotenoid Dioxygenase Cisgene in Grapevine Increases Drought Tolerance and Results in Pleiotropic Effects.

Front Plant Sci 2018 3;9:970. Epub 2018 Aug 3.

Department of Viticulture and Enology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

9--epoxycarotenoid dioxygenase (NCED) is a key enzyme involved in the biosynthesis of abscisic acid (ABA), which is associated with drought tolerance in plants. An osmotic-inducible gene was isolated from a drought-resistant cultivar of and constitutively overexpressed in a drought-sensitive cultivar of . Transgenic plants showed significantly improved drought tolerance, including a higher growth rate and better drought resistant under drought conditions, compared to those of wild-type (WT) plants. After water was withheld for 50 days, the upper leaves of transgenic plants remained green, whereas most leaves of WT plants turned yellow and fell. Besides the increase in ABA content, overexpression of induced the production of jasmonic acid (JA) and accumulation of JA biosynthesis-related genes, including () and (). Moreover, transgenic plants possessed advantageous physiological indices, including lower leaf stomatal density, lower photosynthesis rate, and lower accumulation of proline and superoxide dismutase (SOD), compared to those of WT plants, indicating increased resistance to drought stress. Quantitative real time polymerase chain reaction (RT-qPCR) analysis revealed that overexpression of enhanced the expression of drought-responsive genes, such as () (), (), () and (). Although the development of transgenic plants was delayed by 4 months than WT plants, because of seed dormancy and abnormal seedlings, the surviving transgenic plants provided a solid method for protection of woody plants from drought stress.
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http://dx.doi.org/10.3389/fpls.2018.00970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085461PMC
August 2018

Self-Assembled Double-Bundle DNA Tetrahedron for Efficient Antisense Delivery.

ACS Appl Mater Interfaces 2018 Jul 9;10(28):23693-23699. Epub 2018 Jul 9.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China.

DNA nanostructures are promising biomaterials capable of arranging multiple functional components with nanometer precision. Here, a double-bundle DNA tetrahedron is rationally designed to integrate with antisense oligonucleotides silencing proto-oncogene c-raf and nuclear targeting peptides. The functionalized DNA tetrahedron can be internalized by A549 cells and assists the delivery of antisense oligonucleotides toward the nucleus to increase the chance to downregulate target mRNA in nucleus and cytoplasm. Antisense strands released from the tetrahedron in response to the intracellular reducing environment can inhibit cell proliferation at a low concentration without transfection reagent. Finally, efficient knockdown of c-raf gene is observed, which verified our design. This designer DNA-based nanocarrier system will open a new avenue for efficient delivery of nucleic acid drugs.
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http://dx.doi.org/10.1021/acsami.8b07889DOI Listing
July 2018

A DNA-Based Nanocarrier for Efficient Gene Delivery and Combined Cancer Therapy.

Nano Lett 2018 06 3;18(6):3328-3334. Epub 2018 May 3.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China.

The efficient delivery of a therapeutic gene into target tissues has remained a major obstacle in realizing a viable gene-based medicine. Herein, we introduce a facile and universal strategy to construct a DNA nanostructure-based codelivery system containing a linear tumor therapeutic gene (p53) and a chemotherapeutic drug (doxorubicin, DOX) for combined therapy of multidrug resistant tumor (MCF-7R). This novel codelivery system, which is structurally similar to a kite, is rationally designed to contain multiple functional groups for the targeted delivery and controlled release of the therapeutic cargoes. The self-assembled DNA nanokite achieves efficient gene delivery and exhibits effective inhibition of tumor growth in vitro and in vivo without apparent systemic toxicity. These structurally and chemically well-defined codelivery nanovectors provide a new platform for the development of gene therapeutics for not only cancer but also a wide range of diseases.
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http://dx.doi.org/10.1021/acs.nanolett.7b04812DOI Listing
June 2018

Cloning, Characterization, and Functional Investigation of VaHAESA from Vitis amurensis Inoculated with Plasmopara viticola.

Int J Mol Sci 2018 Apr 16;19(4). Epub 2018 Apr 16.

The Viticulture and Enology Program, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Plant pattern recognition receptors (PRRs) are essential for immune responses and establishing symbiosis. Plants detect invaders via the recognition of pathogen-associated molecular patterns (PAMPs) by PRRs. This phenomenon is termed PAMP-triggered immunity (PTI). We investigated disease resistance in to identify PRRs that are important for resistance against downy mildew, analyzed the PRRs that were upregulated by incompatible infection, and cloned the full-length cDNA of the gene. We then analyzed the structure, subcellular localization, and relative disease resistance of . and PRR-receptor-like kinase 5 (RLK5) are highly similar, belonging to the leucine-rich repeat (LRR)-RLK family and localizing to the plasma membrane. The expression of PRR genes changed after the inoculation of with compatible and incompatible ; during early disease development, transiently transformed plants expressing were more resistant to pathogens than those transformed with the empty vector and untransformed controls, potentially due to increased H₂O₂, NO, and callose levels in the transformants. Furthermore, transgenic showed upregulated expression of genes related to the PTI pathway and improved disease resistance. These results show that is a positive regulator of resistance against downy mildew in grapevines.
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http://dx.doi.org/10.3390/ijms19041204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979312PMC
April 2018

A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo.

Nat Biotechnol 2018 03 12;36(3):258-264. Epub 2018 Feb 12.

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

Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot. The thrombin inside is thus exposed and activates coagulation at the tumor site. Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth. The nanorobot proved safe and immunologically inert in mice and Bama miniature pigs. Our data show that DNA nanorobots represent a promising strategy for precise drug delivery in cancer therapy.
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http://dx.doi.org/10.1038/nbt.4071DOI Listing
March 2018

Author Correction: Nanoparticle-mediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours.

Nat Biomed Eng 2017 08;1(8):680

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

In the version of the Supplementary Information originally published, in Supplementary Fig. 8a, in the bottom row, the left-most image ('Control') was not the correct image; this has now been replaced.
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http://dx.doi.org/10.1038/s41551-017-0125-6DOI Listing
August 2017

Nanoparticle-mediated local depletion of tumour-associated platelets disrupts vascular barriers and augments drug accumulation in tumours.

Nat Biomed Eng 2017 Aug 24;1(8):667-679. Epub 2017 Jul 24.

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

Limited intratumoural perfusion and nanoparticle retention remain major bottlenecks for the delivery of nanoparticle therapeutics into tumours. Here, we show that polymer-lipid-peptide nanoparticles delivering the antiplatelet antibody R300 and the chemotherapeutic agent doxorubicin can locally deplete tumour-associated platelets, thereby enhancing vascular permeability and augmenting the accumulation of the nanoparticles in tumours. R300 is specifically released in the tumour on cleavage of the lipid-peptide shell of the nanoparticles by matrix metalloprotease 2, which is commonly overexpressed in tumour vascular endothelia and stroma, thus facilitating vascular breaches that enhance tumour permeability. We also show that this strategy leads to substantial tumour regression and metastasis inhibition in mice.
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http://dx.doi.org/10.1038/s41551-017-0115-8DOI Listing
August 2017

Phytohormone and genome variations in Vitis amurensis resistant to downy mildew.

Genome 2017 Oct 20;60(10):791-796. Epub 2017 Jul 20.

b College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Downy mildew (DM) resistance is a highly desirable agronomic trait in grape breeding. High variation in Plasmopara viticola resistance was found in Vitis cultivars. Some accessions show high P. viticola resistance even under conditions highly conducive to DM. Here, leaf disc inoculation experiments revealed that Vitis amurensis 'Zuoshaner' exhibited DM resistance with necrotic spots, whereas the V. amurensis × V. vinifera hybrid cultivar 'Zuoyouhong' was susceptible. Changes in plant hormones accumulation profiles differed between the cultivars. To investigate the genetic mechanisms related to DM resistance, we performed genome-wide sequencing of 'Zuoshaner' and 'Zuoyouhong' and identified cultivar-specific single-nucleotide polymorphisms, insertions/deletions (indels), structural variations (SVs), and copy number variations (CNVs), identifying 5399 SVs and 191 CNVs specific for 'Zuoshaner'. Genes affected by these genetic variations were enriched in biological processes, including defense response and response to stress and stimulation, and were associated with sesquiterpenoid and triterpenoid biosynthesis, ABC transporters, and phenylalanine metabolism pathways. Additionally, indels and SVs were detected in six NBS-LRR disease resistance genes, and a CNV was mapped to the Rpv8 locus responsible for downy mildew resistance. These findings further our understanding of the genetic mechanisms underlying grape mildew resistance, and will facilitate genomic marker-assisted breeding for improved V. amurensis cultivars.
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http://dx.doi.org/10.1139/gen-2017-0008DOI Listing
October 2017

A combinatorial strategy using YAP and pan-RAF inhibitors for treating KRAS-mutant pancreatic cancer.

Cancer Lett 2017 08 30;402:61-70. Epub 2017 May 30.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, 11 Beiyitiao, Zhongguancun, Beijing 100190, China. Electronic address:

KRAS mutation is the most common genetic event in pancreatic cancer. Whereas KRAS itself has proven difficult to inhibit, agents that target key downstream signals of KRAS, such as RAF, are possibly effective for pancreatic cancer treatment. Because selective BRAF inhibitors paradoxically induce downstream signaling activation, a pan-RAF inhibitor, LY3009120 is a better alternate for KRAS-mutant tumor treatment. Here we explored a new combinational strategy using a YAP inhibitor and LY3009120 in pancreatic cancer treatment. We found that reduced YAP expression closely correlates with longer relapse-free and overall survival of patients. Stable knockdown of YAP significantly inhibited pancreatic cancer cell proliferation and tumor growth. In addition, LY3009120 exhibited a dramatically enhanced antitumor effect in combination with YAP knockdown. YAP depletion blocks the activation of a parallel AKT signal pathway after LY3009120 treatment. Finally, combination with a YAP inhibitor, verteporfin, significantly enhanced the antitumor efficacy of LY3009120. Collectively, our results demonstrate that genetic or pharmacological inhibition of YAP can increase sensitivity to LY3009120 in pancreatic cancer through blocking compensatory activation of a parallel AKT signal pathway, thereby validating a combinatorial approach for treating KRAS-mutant pancreatic cancer.
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http://dx.doi.org/10.1016/j.canlet.2017.05.015DOI Listing
August 2017

Self-Assembled DNA Dendrimer Nanoparticle for Efficient Delivery of Immunostimulatory CpG Motifs.

ACS Appl Mater Interfaces 2017 Jun 6;9(24):20324-20329. Epub 2017 Jun 6.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology , 11 BeiYiTiao, ZhongGuanCun, 100190 Beijing, China.

Dendrimer-like DNA nanostructures have attractive properties such as mechanical stability, highly branched nanostructure, customized sizes, and biocompatibility. In this study, we construct programmable DNA dendrimeric nanoparticles as efficient vehicles to deliver immunostimulatory cytosine-phosphate-guanosine (CpG) sequences for activation of the immune response. DNA dendrimers decorated with CpG-containing hairpin-loops triggered stronger immune response characterized by pro-inflammatory cytokines production, in contrast to DNA dendrimers loading linear CpG. After further modification with TAT peptide, a typical cell-penetrating peptide, on the surface of the nanocarriers, CpG loops-loaded DNA dendrimers showed the enhanced cell internalization and cytokines production. The TAT-DNA dendrimer-CpG loops constructs did not affect the viability of immune cells and no detectable cytotoxicity was observed. Our results demonstrate that the DNA dendrimers can serve as designable and safe vehicles for delivery of immune modulators and anticancer drugs.
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http://dx.doi.org/10.1021/acsami.7b05890DOI Listing
June 2017