Publications by authors named "Chunhai Fan"

486 Publications

Addition-Elimination Mechanism-Activated Nucleotide Transition Sequencing for RNA Dynamics Profiling.

Anal Chem 2021 Oct 6. Epub 2021 Oct 6.

Institute of Analytical Chemistry and Instrument for Life Science, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xianning West Road, Xi'an, Shaanxi 710049, China.

Dynamic information of intracellular transcripts is essential to understand their functional roles. Routine RNA-sequencing (RNA-seq) methods only measure RNA species at a steady state and do not provide RNA dynamic information. Here, we develop addition-elimination mechanism-activated nucleotide transition sequencing (AENT-seq) for transcriptome-wide profiling of RNA dynamics. In AENT-seq, nascent transcripts are metabolically labeled with 4-thiouridine (4sU). The total RNA is treated with NH·HO under aqueous conditions. NH·HO is demonstrated to convert 4sU to 4-hydrazino cytosine (C*) based on an addition-elimination chemistry. C* is regarded as cytosine (C) during the DNA extension process. This 4sU-to-C transition marks nascent transcripts, so it enables sequencing analysis of RNA dynamics. We apply our AENT-seq to investigate transcript dynamic information of several genes involved in cancer progression and metastasis. This method uses a simple chemical reaction in aqueous solutions and will be rapidly disseminated with extensive applications.
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http://dx.doi.org/10.1021/acs.analchem.1c03361DOI Listing
October 2021

Optically Controlled Ultrafast Terahertz Metadevices with Ultralow Pump Threshold.

Small 2021 Oct 5:e2104275. Epub 2021 Oct 5.

School of Physics, Peking University, Beijing, 100871, China.

Arming metasurface with active materials furnishes a feasible solution to dynamically control over terahertz (THz) waves, which is extremely significant for the realization of upcoming sixth generation telecommunications. However, the present active materials are mainly limited to single external driving field, hindering the capability of metasurface for flexible manipulation of THz waves. Besides, less attention has been paid to the energy question how to significantly reduce the pump threshold for achieving the desired function. Here, a germanium (Ge) hybrid Fano metasurface under dual-stimulus control is experimentally demonstrated. Photoexcitation of Ge thin film enables 100% modulation depth of Fano resonance and ultrafast switching time within 10 ps. By adding current-bias, the pump threshold to modulate the metasurface is greatly reduced from 1600 to 200 µJ cm . Different from the optical modulation independent of film thickness, it is found that the current function is in proportion with the thickness of Ge thin film. Moreover, it is demonstrated that compared to the single optical-stimulus, the THz amplitude modulation is increased by 56.3% under dual-stimulus function. This work naturally improves the flexibility and practicality of Ge-based metadevice and inspires more innovations to boost the development of switchable sensing, lasing spacer, and nonlinear systems.
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http://dx.doi.org/10.1002/smll.202104275DOI Listing
October 2021

Modular DNA Circuits for Point-of-Care Colorimetric Assay of Infectious Pathogens.

Anal Chem 2021 Sep 10. Epub 2021 Sep 10.

State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.

Accurate, specific, and inexpensive detection of multiple infectious pathogens simultaneously is a significant goal for human health and safety. Herein we present a rationally designed modular DNA circuit for point-of-care (POC) detection of a variety of infectious pathogens based on nucleic acid isothermal amplification technology and DNAzyme-mediated colorimetric readout. A modular DNA circuit was constructed with a fixed module and a flexible module and was rationally designed according to genetic targets. On this basis, the platform could detect multiple genetic targets corresponding to infectious pathogens simultaneously. Signal amplification properties of the DNA circuit and the peroxidase-like DNAzyme enable the detection limits to reach the picomolar level. By urea treatment and magnetic separation, the fixed module can be reused at least five times, which makes this assay more economical and environmentally friendly. The detection of genetic infectious pathogens should be accomplished in 2 h with naked-eye observation and may provide an efficient tool for POC analysis of multiple infectious pathogens, especially in resource-poor areas.
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http://dx.doi.org/10.1021/acs.analchem.1c02597DOI Listing
September 2021

Reconstructing Soma-Soma Synapse-like Vesicular Exocytosis with DNA Origami.

ACS Cent Sci 2021 Aug 28;7(8):1400-1407. Epub 2021 Jul 28.

Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Cell-cell communications exhibit distinct physiological functions in immune responses and neurotransmitter signaling. Nevertheless, the ability to reconstruct a soma-soma synapse-like junction for probing intercellular communications remains difficult. In this work, we develop a DNA origami nanostructure-based method for establishing cell conjugation, which consequently facilitates the reconstruction of a soma-soma synapse-like junction. We demonstrate that intercellular communications including small molecule and membrane vesicle exchange between cells are maintained in the artificially designed synapse-like junction. By inserting the carbon fiber nanometric electrodes into the soma-soma synapse-like junction, we accomplish the real-time monitoring of individual vesicular exocytotic events and obtain the information on vesicular exocytosis kinetics via analyzing the parameters of current spikes. This strategy provides a versatile platform to study synaptic communications.
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http://dx.doi.org/10.1021/acscentsci.1c00645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393203PMC
August 2021

DNA Assembly-Based Stimuli-Responsive Systems.

Adv Sci (Weinh) 2021 07 14;8(13):2100328. Epub 2021 May 14.

School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules Institute of Translational Medicine Shanghai Jiao Tong University Shanghai 200240 China.

Stimuli-responsive designs with exogenous stimuli enable remote and reversible control of DNA nanostructures, which break many limitations of static nanostructures and inspired development of dynamic DNA nanotechnology. Moreover, the introduction of various types of organic molecules, polymers, chemical bonds, and chemical reactions with stimuli-responsive properties development has greatly expand the application scope of dynamic DNA nanotechnology. Here, DNA assembly-based stimuli-responsive systems are reviewed, with the focus on response units and mechanisms that depend on different exogenous stimuli (DNA strand, pH, light, temperature, electricity, metal ions, etc.), and their applications in fields of nanofabrication (DNA architectures, hybrid architectures, nanomachines, and constitutional dynamic networks) and biomedical research (biosensing, bioimaging, therapeutics, and theranostics) are discussed. Finally, the opportunities and challenges for DNA assembly-based stimuli-responsive systems are overviewed and discussed.
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http://dx.doi.org/10.1002/advs.202100328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261508PMC
July 2021

Nucleic Acid Tests for Clinical Translation.

Chem Rev 2021 Sep 13;121(17):10469-10558. Epub 2021 Jul 13.

Institute of Molecular Medicine, Department of Liver Surgery, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information. Overexpressed or underexpressed as well as mutated nucleic acids have been implicated in many diseases. Therefore, nucleic acid tests (NATs) are extremely important. Inspired by intracellular DNA replication and RNA transcription, NATs have been extensively developed to improve the detection specificity, sensitivity, and simplicity. The principles of NATs can be in general classified into three categories: nucleic acid hybridization, thermal-cycle or isothermal amplification, and signal amplification. Driven by pressing needs in clinical diagnosis and prevention of infectious diseases, NATs have evolved to be a rapidly advancing field. During the past ten years, an explosive increase of research interest in both basic research and clinical translation has been witnessed. In this review, we aim to provide comprehensive coverage of the progress to analyze nucleic acids, use nucleic acids as recognition probes, construct detection devices based on nucleic acids, and utilize nucleic acids in clinical diagnosis and other important fields. We also discuss the new frontiers in the field and the challenges to be addressed.
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http://dx.doi.org/10.1021/acs.chemrev.1c00241DOI Listing
September 2021

Encoding Fluorescence Anisotropic Barcodes with DNA Fameworks.

J Am Chem Soc 2021 Jul 9;143(28):10735-10742. Epub 2021 Jul 9.

Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.

Fluorescence anisotropy (FA) holds great potential for multiplexed analysis and imaging of biomolecules since it can effectively discriminate fluorophores with overlapping emission spectra. Nevertheless, its susceptibility to environmental variation hampers its widespread applications in biology and biotechnology. In this study, we design FA DNA frameworks (FAFs) by scaffolding fluorophores in a fluorescent protein-like microenvironment. We find that the FA stability of the fluorophores is remarkably improved due to the sequestration effects of FAFs. The FA level of the fluorophores can be finely tuned when placed at different locations on an FAF, analogous to spectral shifts of protein-bound fluorophores. The high programmability of FAFs further enables the design of a spectrum of encoded FA barcodes for multiplexed sensing of nucleic acids and multiplexed labeling of live cells. This FAF system thus establishes a new paradigm for designing multiplexing FA probes for cellular imaging and other biological applications.
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http://dx.doi.org/10.1021/jacs.1c04942DOI Listing
July 2021

Asymmetric reconstruction of mammalian reovirus reveals interactions among RNA, transcriptional factor µ2 and capsid proteins.

Nat Commun 2021 07 7;12(1):4176. Epub 2021 Jul 7.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.

Mammalian reovirus (MRV) is the prototypical member of genus Orthoreovirus of family Reoviridae. However, lacking high-resolution structures of its RNA polymerase cofactor μ2 and infectious particle, limits understanding of molecular interactions among proteins and RNA, and their contributions to virion assembly and RNA transcription. Here, we report the 3.3 Å-resolution asymmetric reconstruction of transcribing MRV and in situ atomic models of its capsid proteins, the asymmetrically attached RNA-dependent RNA polymerase (RdRp) λ3, and RdRp-bound nucleoside triphosphatase μ2 with a unique RNA-binding domain. We reveal molecular interactions among virion proteins and genomic and messenger RNA. Polymerase complexes in three Spinoreovirinae subfamily members are organized with different pseudo-D symmetries to engage their highly diversified genomes. The above interactions and those between symmetry-mismatched receptor-binding σ1 trimers and RNA-capping λ2 pentamers balance competing needs of capsid assembly, external protein removal, and allosteric triggering of endogenous RNA transcription, before, during and after infection, respectively.
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http://dx.doi.org/10.1038/s41467-021-24455-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263624PMC
July 2021

Protein-Mimicking Nanoparticles for a Cellular Regulation of Homeostasis.

ACS Appl Mater Interfaces 2021 Jul 6;13(27):31331-31336. Epub 2021 Jul 6.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.

The distinct physical and chemical properties of nanoparticles (NPs) offer great opportunities to develop new strategies for diagnostic and therapeutic purposes. Whereas NPs often serve as inert nanocarriers, their inherent "biological" activities have recently been extensively unveiled and explored. These protein-mimicking NPs (dubbed protmins) have been reported to modulate a cellular homeostasis without displaying a general toxicity, which may act as potential nanomedicines to provide a monotherapy or combination therapy in a disease treatment. In the meanwhile, the unexpected behaviors of protmins in complex biological systems also raise new concerns on the biosafety issue. Herein, we summarize several categories of the protmin-based regulation of cellular homeostasis and discuss their broad effects on cell functions and behaviors.
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http://dx.doi.org/10.1021/acsami.1c09281DOI Listing
July 2021

Remote Photothermal Control of DNA Origami Assembly in Cellular Environments.

Nano Lett 2021 07 16;21(13):5834-5841. Epub 2021 Jun 16.

The Interdisciplinary Research Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.

In situ synthesis of DNA origami structures in living systems is highly desirable due to its potential in biological applications, which nevertheless is hampered by the requirement of thermal activation procedures. Here, we report a photothermal DNA origami assembly method in near-physiological environments. We find that the use of copper sulfide nanoparticles (CuS NPs) can mediate efficient near-infrared (NIR) photothermal conversion to remotely control the solution temperature. Under a 4 min NIR illumination and subsequent natural cooling, rapid and high-yield (>80%) assembly of various types of DNA origami nanostructures is achieved as revealed by atomic force microscopy and single-molecule fluorescence resonance energy transfer analysis. We further demonstrate the in situ assembly of DNA origami with high location precision in cell lysates and in cell culture environments.
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http://dx.doi.org/10.1021/acs.nanolett.1c01821DOI Listing
July 2021

Prescribing Silver Chirality with DNA Origami.

J Am Chem Soc 2021 Jun 3;143(23):8639-8646. Epub 2021 Jun 3.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.

Metal nanostructures of chiral geometry interacting with light via surface plasmon resonances can produce tailorable optical activity with their structural alterations. However, bottom-up fabrication of arbitrary chiral metal nanostructures with precise size and morphology remains a synthetic challenge. Here we develop a DNA origami-enabled aqueous solution metallization strategy to prescribe the chirality of silver nanostructures in three dimensions. We find that diamine silver(I) complexes coordinate with the bases of prescribed single-stranded protruding clustered DNA (pcDNA) on DNA origami via synergetic interactions including coordination, hydrogen bonds, and ion-π interaction, which induce site-specific pcDNA condensation and local enrichment of silver precursors that lowers the activation energy for nucleation. Using tubular DNA origami-based metallization, we obtain helical silver patterns up to a micrometer in length with well-defined chirality and pitches. We further demonstrate tailorable plasmonic optical activity of metallized chiral silver nanostructures. This method opens new pathways to synthesize programmable inorganic materials with arbitrary morphology and chirality.
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http://dx.doi.org/10.1021/jacs.1c00363DOI Listing
June 2021

DNA origami single crystals with Wulff shapes.

Nat Commun 2021 05 21;12(1):3011. Epub 2021 May 21.

National Laboratory of Solid State Microstructures, College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, China.

DNA origami technology has proven to be an excellent tool for precisely manipulating molecules and colloidal elements in a three-dimensional manner. However, fabrication of single crystals with well-defined facets from highly programmable, complex DNA origami units is a great challenge. Here, we report the successful fabrication of DNA origami single crystals with Wulff shapes and high yield. By regulating the symmetries and binding modes of the DNA origami building blocks, the crystalline shapes can be designed and well-controlled. The single crystals are then used to induce precise growth of an ultrathin layer of silica on the edges, resulting in mechanically reinforced silica-DNA hybrid structures that preserve the details of the single crystals without distortion. The silica-infused microcrystals can be directly observed in the dry state, which allows meticulous analysis of the crystal facets and tomographic 3D reconstruction of the single crystals by high-resolution electron microscopy.
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http://dx.doi.org/10.1038/s41467-021-23332-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140131PMC
May 2021

Sequential Therapy of Acute Kidney Injury with a DNA Nanodevice.

Nano Lett 2021 05 17;21(10):4394-4402. Epub 2021 May 17.

Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

The high demand for acute kidney injury (AKI) therapy calls the development of multifunctional nanomedicine for renal management with programmable pharmacokinetics. Here, we developed a renal-accumulating DNA nanodevice with exclusive kidney retention for longitudinal protection of AKI in different stages in a renal ischemia-reperfusion (I/R) model. Due to the prolonged kidney retention time (>12 h), the ROS-sensitive nucleic acids of the nanodevice could effectively alleviate oxidative stress by scavenging ROS in stage I, and then the anticomplement component 5a (aC5a) aptamer loaded nanodevice could sequentially suppress the inflammatory responses by blocking C5a in stage II, which is directly related to the cytokine storm. This sequential therapy provides durable and pathogenic treatment of kidney dysfunction based on successive pathophysiological events induced by I/R, which holds great promise for renal management and the suppression of the cytokine storm in more broad settings including COVID-19.
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http://dx.doi.org/10.1021/acs.nanolett.1c01044DOI Listing
May 2021

DNA Framework-Engineered Long-Range Electrostatic Interactions for DNA Hybridization Reactions.

Angew Chem Int Ed Engl 2021 07 18;60(30):16693-16699. Epub 2021 Jun 18.

School of Chemistry and Chemical Engineering, Frontiers Science Centre for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, China.

Long-range electrostatic interactions beyond biomolecular interaction interfaces have not been extensively studied due to the limitation in engineering electric double layers in physiological fluids. Here we find that long-range electrostatic interactions play an essential role in kinetic modulation of DNA hybridizations. Protein and gold nanoparticles with different charges are encapsulated in tetrahedral frameworks to exert diverse electrostatic effects on site-specifically tethered single DNA strands. Using this strategy, we have successfully modulated the hybridization kinetics in both bulk solution and single molecule level. Experimental and theoretical studies reveal that long-range Coulomb interactions are the key factor for hybridization rates. This work validates the important role of long-range electrostatic forces in nucleic acid-biomacromolecule complexes, which may encourage new strategies of gene regulation, antisense therapy, and nucleic acid detection.
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http://dx.doi.org/10.1002/anie.202106010DOI Listing
July 2021

An Oligonucleotide-Distortion-Responsive Organic Transistor for Platinum-Drug-Induced DNA-Damage Detection.

Adv Mater 2021 Jun 13;33(25):e2100489. Epub 2021 May 13.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Organic transistor with DNA-damage evaluation ability can open up novel opportunities for bioelectronic devices. Even though trace amounts of drugs can cause cumulative gene damage in vivo, the extremely low occurrence proportion makes them hardly transduced into detectable electric signals. Here, an ultrasensitive DNA-damage sensor based on an oligonucleotide-distortion-responsive organic transistor (DROT) is reported by creating controllable conformation change of double-stranded DNA on the surface of organic semiconductors. In combination with interfacial charge redistribution and efficient signal amplification, the DROT provides an ultrasensitive single-site DNA-damage response with 20.5 s even upon 1 × 10 m cisplatin. The high generalizability of this DROT to three generations of classical platinum drugs and gene-relevant DNA damage is demonstrated. A biochip is further designed for intelligent damage analysis in complex environments, which holds the potential for high-throughput biotoxicity evaluation and drug screening in the future.
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http://dx.doi.org/10.1002/adma.202100489DOI Listing
June 2021

A nano-integrated microfluidic biochip for enzyme-based point-of-care detection of creatinine.

Chem Commun (Camb) 2021 May;57(38):4726-4729

Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, P. R. China. and University of Chinese Academy of Sciences, Beijing 100049, P. R. China and Institute of Molecular Medicine, Renji Hospital, School of Medicine and School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200127, P. R. China.

A nano-integrated portable enzymatic microfluidic electrochemical biochip was developed for single-step point-of-care testing of creatinine. The biochip could automatically eliminate a lot of interferences from practical biological samples and enzymatic intermediate products. Gold nanostructure- and carbon nanotube-based screen-printed carbon electrodes were integrated into microfluidic structures to improve the detection performance for creatinine. The microfluidic electrochemical biochip holds promise to become a practical device for medical diagnosis, especially POCT.
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http://dx.doi.org/10.1039/d1cc00825kDOI Listing
May 2021

Metal-Bridged Graphene-Protein Supraparticles for Analog and Digital Nitric Oxide Sensing.

Adv Mater 2021 Jun 7;33(24):e2007900. Epub 2021 May 7.

School of Chemistry and Chemical Engineering and Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200241, China.

Self-limited nanoassemblies, such as supraparticles (SPs), can be made from virtually any nanoscale components, but SPs from nanocarbons including graphene quantum dots (GQDs), are hardly known because of the weak van der Waals attraction between them. Here it is shown that highly uniform SPs from GQDs can be successfully assembled when the components are bridged by Tb ions supplementing van der Waals interactions. Furthermore, they can be coassembled with superoxide dismutase, which also has weak attraction to GQDs. Tight structural integration of multilevel components into SPs enables efficient transfer of excitonic energy from GQDs and protein to Tb . This mechanism is activated when Cu is reduced to Cu by nitric oxide (NO)-an important biomarker for viral pulmonary infections and Alzheimer's disease. Due to multipronged fluorescence enhancement, the limit of NO detection improves 200 times reaching 10 × 10 m. Furthermore, the uniform size of SPs enables digitization of the NO detection using the single particle detection format resulting in confident registration of as few as 600 molecules mL . The practicality of the SP-based assay is demonstrated by the successful monitoring of NO in human breath. The biocompatible SPs combining proteins, carbonaceous nanostructures, and ionic components provide a general path for engineering uniquely sensitive assays for noninvasive tracking of infections and other diseases.
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http://dx.doi.org/10.1002/adma.202007900DOI Listing
June 2021

General Synthesis of Ultrafine Monodispersed Hybrid Nanoparticles from Highly Stable Monomicelles.

Adv Mater 2021 Jun 29;33(23):e2100820. Epub 2021 Apr 29.

Department of Chemistry, Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, iChEM and State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, 200433, P. R. China.

Ultrafine nanoparticles with organic-inorganic hybridization have essential roles in myriad applications. Over the past three decades, although various efforts on the formation of organic or inorganic ultrasmall nanoparticles have been made, ultrafine organic-inorganic hybrid nanoparticles have scarcely been achieved. Herein, a family of ultrasmall hybrid nanoparticles with a monodisperse, uniform size is synthesized by a facile thermo-kinetics-mediated copolymer monomicelle approach. These thermo-kinetics-mediated monomicelles with amphiphilic ABC triblock copolymers are structurally robust due to their solidified polystyrene core, endowing them with ultrahigh thermodynamic stability, which is difficult to achieve using Pluronic surfactant-based micelles (e.g., F127). This great stability combined with a core-shell-corona structure makes the monodispersed monomicelles a robust template for the precise synthesis of ultrasmall hybrid nanoparticles with a highly uniform size. As a demonstration, the obtained micelles/SiO hybrid nanoparticles display ultrafine sizes, excellent uniformity, monodispersity, and tunable structural parameters (diameters: 24-47 nm and thin shell thickness: 2.0-4.0 nm). Notably, this approach is universal for creating a variety of multifunctional ultrasmall hybrid nanostructures, involving organic/organic micelle/polymers (polydopamine) nanoparticles, organic/inorganic micelle/metal oxides (ZnO, TiO , Fe O ), micelle/hydroxides (Co(OH) ), micelle/noble metals (Ag), and micelle/TiO /SiO hybrid composites. As a proof of concept, the ultrasmall micelle/SiO hybrid nanoparticles demonstrate superior toughness as biomimetic materials.
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http://dx.doi.org/10.1002/adma.202100820DOI Listing
June 2021

Proteomic Exploration of Endocytosis of Framework Nucleic Acids.

Small 2021 06 24;17(23):e2100837. Epub 2021 Apr 24.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

Efficient cell internalization of framework nucleic acid nanostructures free of transfection agents provides new opportunities for developing biocompatible and intelligent nanoprobes and drug delivery carriers. Here, a proteomic identification method to screen target proteins that interact with tetrahedral DNA nanostructures (TDNs) during the process of endocytosis by combining drug affinity responsive target stability (DARTS) with liquid chromatography/tandem mass spectrometry (LC-MS/MS) techniques, is reported. It is found that that caveolin-1 (CAV1) and macropinocytosis-related protein sorting nexin5 (SNX5) are associated with the endocytosis of TNDs, which is further validated by microscale thermophoresis (MST) analysis. CAV1- and SNX5- knockout experiments reveal that both caveolae-mediated endocytosis and macropinocytosis mediate the cellular uptake of TDNs, which complement previous findings with fluorescence tracing methods. This method provides a generic strategy to analyze cellular internalization process of DNA nanostructures for biomedical applications.
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http://dx.doi.org/10.1002/smll.202100837DOI Listing
June 2021

Multi-Mode Reconfigurable DNA-Based Chemical Reaction Circuits for Soft Matter Computing and Control.

Angew Chem Int Ed Engl 2021 06 1;60(27):15013-15019. Epub 2021 Jun 1.

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.

Developing smart material systems for performing different tasks in diverse environments remains challenging. Here, we show that by integrating stimuli-responsive soft materials with multi-mode reconfigurable DNA-based chemical reaction circuits (D-CRCs), it can control size change of microgels with multiple reaction pathways and adapt expansion behaviors to meet diverse environments. We first use pH-responsive intramolecular conformational switches for regulating DNA strand displacement reactions (SDRs). The ability to regulate SDRs with tunable pH-dependence allows to build dynamic chemical reaction networks with diverse reaction pathways. We confirm that the designed DNA switching circuits are reconfigurable at different pH and perform different logic operations, and the swelling of DNA switching circuit-integrated microgel systems can be programmably directed by D-CRCs. Our approach provides insight into building smart responsive materials and fabricating autonomous soft robots.
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http://dx.doi.org/10.1002/anie.202102169DOI Listing
June 2021

Probing the Formation Kinetics and Thermodynamics with Rationally Designed Analytical Tools Enables One-Pot Synthesis and Purification of a Tetrahedral DNA Nanostructure.

Anal Chem 2021 05 22;93(18):7045-7053. Epub 2021 Apr 22.

Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Analytical & Testing Center, Sichuan University, Chengdu, Sichuan 610064, P. R. China.

The development of robust analytical tools capable of probing the formation kinetics and thermodynamics of DNA nanostructures is a crucial step toward better understanding and manufacturing of diverse DNA-based materials. Herein, we introduce a real-time fluorescence anisotropy assay and rationally designed DNA reaction termination probes (DRTPs) as a set of new tools for exploring the formation mechanisms of DNA nanostructures. We deployed these tools for probing the formation of a classic tetrahedral DNA nanostructure (TDN) as a model system. Our tools revealed that the formation of TDN was dominated by simultaneous hybridization, whereas its undesired side products were caused mainly through step-wise hybridization. An optimal reaction temperature exists that favors the formation of TDN over side products. With insight into the TDN formation mechanism, we further engineered magnetic DRTPs to achieve single-step purification of TDN, enabling 10-fold improvement in the ratio between the targeted TDN and undesired side products without tedious procedures or bulky instruments. Combining the optimal reaction and purification conditions, we finally demonstrated the one-pot synthesis and purification of TDN. The analytical techniques offered in this work may hold potential to find wide applications and inspire new analytical methods for structural DNA nanotechnology.
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http://dx.doi.org/10.1021/acs.analchem.1c00363DOI Listing
May 2021

Hydrophobic collapse-driven nanoparticle coating with poly-adenine adhesives.

Chem Commun (Camb) 2021 Apr 19;57(31):3801-3804. Epub 2021 Mar 19.

Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China.

The mechanism underlying the strong adhesion between DNA with consecutive adenines (polyA) and Au nanoparticles (AuNPs) is experimentally and theoretically studied. We elucidate that the consecutive adenines collectively result in hydrophobic collapse in the adhesion process, which plays a pivotal role for the high adhesion affinity and specificity.
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http://dx.doi.org/10.1039/d1cc00628bDOI Listing
April 2021

Biocomputing Based on DNA Strand Displacement Reactions.

Chemphyschem 2021 06 20;22(12):1151-1166. Epub 2021 May 20.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 201240, China.

The high sequence specificity and precise base complementary pairing principle of DNA provides a rich orthogonal molecular library for molecular programming, making it one of the most promising materials for developing bio-compatible intelligence. In recent years, DNA has been extensively studied and applied in the field of biological computing. Among them, the toehold-mediated strand displacement reaction (SDR) with properties including enzyme free, flexible design and precise control, have been extensively used to construct biological computing circuits. This review provides a systemic overview of SDR design principles and the applications. Strategies for designing DNA-only, enzymes-assisted, other molecules-involved and external stimuli-controlled SDRs are described. The recently realized computing functions and the application of DNA computing in other fields are introduced. Finally, the advantages and challenges of SDR-based computing are discussed.
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http://dx.doi.org/10.1002/cphc.202100140DOI Listing
June 2021

Poly-Adenine-Based Spherical Nucleic Acids for Efficient Live-Cell MicroRNA Capture.

Angew Chem Int Ed Engl 2021 06 24;60(26):14438-14445. Epub 2021 May 24.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

Direct delivery of exogenous non-coding nucleic acids into living cells has attracted intense interest in biological applications. However, the cell entry efficiency and target capture ability remain to be improved. Herein, we report a method for compartmenting the nucleic acids on the surface of poly-adenine-based spherical nucleic acids (polyA-SNAs) for efficient capture of oncogenic microRNAs (miRNAs) in living cells. We find that polyA-SNAs exhibit high cell entry efficiency, which is insensitive to the configuration of the anti-miRNA sequences. By programming the length of polyAs, we precisely engineered the spatial configuration of the anti-miRNA sequences in polyA-SNAs. Compartmentalized polyA-SNAs bind to miRNAs with improved capture ability as compared to densely compacted SNAs. We further demonstrate that polyA-SNAs serve as high-efficacy miRNA sponges for capturing oncogenic miRNAs both in living cells and in mice. The efficient inhibition of miRNAs results in significant suppression of tumor growth.
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http://dx.doi.org/10.1002/anie.202017039DOI Listing
June 2021

Precisely Controlled Vertical Alignment in Mesostructured Carbon Thin Films for Efficient Electrochemical Sensing.

ACS Nano 2021 Apr 6;15(4):7713-7721. Epub 2021 Apr 6.

Laboratory of Advanced Materials, Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Fudan University, Shanghai 200433, People's Republic of China.

Two-dimensional carbon materials, incorporating a large mesoporosity, are attracting considerable research interest in various fields such as catalysis, electrochemistry, and energy-related technologies owing to their integrated functionalities. However, their potential applications, which require favorable mass transport within mesopore channels, are constrained by the undesirable and finite mesostructural configurations due to the immense synthetic difficulties. Herein, we demonstrate an oriented monomicelle assembly strategy, for the facile fabrication of highly ordered mesoporous carbon thin films with vertically aligned and permeable mesopore channels. Such a facile and reproducible approach relies on the swelling and fusion effect of hydrophobic benzene homologues for directional monomicelle assembly. The orientation assembly process shows precise controllability and great universality, affording mesoporous carbon films with a cracking-free structure over a centimeter in size, highly tunable thicknesses (13 to 85 nm, an interval of ∼12 nm), mesopore size (8.4 to 13.5 nm), and switchable growth substrates. Owing to their large permeable mesopore channels, electrochemical sensors based on vertical mesoporous carbon films exhibit an ultralow limit of detection (50 nmol L) and great sensitivity in dopamine detection.
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http://dx.doi.org/10.1021/acsnano.1c01367DOI Listing
April 2021

Epigenetic Remodeling Hydrogel Patches for Multidrug-Resistant Triple-Negative Breast Cancer.

Adv Mater 2021 May 1;33(18):e2100949. Epub 2021 Apr 1.

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

The induced expansion of tumor-initiating cells (T-ICs) upon repeated exposure of tumors to chemotherapeutic drugs forms a major cause for chemoresistance and cancer metastasis. Here, a tumor-microenvironment-responsive hydrogel patch is designed to modulate the plasticity of T-ICs in triple-negative breast cancer (TNBC), which is insensitive to hormone- and HER2-targeting. The on-site formation of the hydrogel network patches tumors in a chemoresistant TNBC murine model and senses intratumoral reactive oxygen species for linker cleavage and payload release. Patch-mediated inhibition of the histone demethylase lysine-specific demethylase 1 (LSD1) epigenetically regulates the switch of T-ICs from self-renewal to differentiation, rehabilitating their chemosensitivity. Moreover, the hydrogel patch enhances tumor immunogenicity and increases T-cell infiltration via epigenetic activation of innate immunity. A single-dose of the hydrogel patch harboring LSD1 inhibitor and chemotherapy agent efficiently suppresses tumor growth, postsurgical relapse, and metastasis. The superior efficacy against multidrug resistance further reveals the broad applicability of epigenetic remodeling hydrogel patches.
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http://dx.doi.org/10.1002/adma.202100949DOI Listing
May 2021

pH- and miRNA-Responsive DNA-Tetrahedra/Metal-Organic Framework Conjugates: Functional Sense-and-Treat Carriers.

ACS Nano 2021 04 31;15(4):6645-6657. Epub 2021 Mar 31.

Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.

The synthesis of stimuli-responsive hybrid structures composed of drug-loaded UiO-66 metal-organic framework nanoparticles, NMOFs, locked by DNA tetrahedra gates is presented. The hybrid systems combine the high loading capacity of drugs in the porous NMOFs and the effective cell permeation properties of the DNA tetrahedra. The nucleic acid-functionalized UiO-66 NMOFs are loaded with drugs (doxorubicin, DOX, or camptothecin, CPT) or with dyes as drug models (Rhodamine 6G or fluorescein) and used to prepare stimuli-responsive carriers. In this study, two different stimuli-responsive NMOFs are presented. One system introduces the drug-loaded NMOFs locked by pH-responsive DNA tetrahedra. At acidic pH values, the gating tetrahedra are dissociated from the NMOFs through the formation of i-motif structures, resulting in the unlocking of the NMOFs and the release of the drugs. In addition, the tetrahedra gates are modified with AS1411 aptamer tethers, and these target the drug-loaded NMOFs to nucleolin receptors overexpressed in certain malignant cells. A second system involves the preparation of NMOFs loaded with drugs/dyes and gated by the microRNA (miRNA)-responsive tetrahedra (miRNA-21 or miRNA-155). In the presence of miRNAs, the dissociation of miRNA-responsive tetrahedra from the NMOFs leads to the unlocking of the NMOFs and the release of the loads. Further developments of the miRNA-responsive tetrahedra-gated hybrid carriers include the following. (i) By appropriate engineering of the miRNA gating units, the exonuclease III (Exo III)-amplified unlocking of the carriers, through the regeneration of the miRNA triggers, and the enhanced release of the loaded drugs are demonstrated. (ii) By applying mixtures of miRNA-21-responsive DNA tetrahedra-gated DOX-loaded NMOFs and miRNA-155-responsive DNA tetrahedra-gated CPT-loaded NMOFs, the multiplexed miRNA-21/miRNA-155-dictated release of the drugs is demonstrated. As compared to the analog DNA duplex-modified NMOFs, DNA tetrahedra-gated, drug-loaded NMOFs permeation into malignant MDA-MB-231 breast cancer cells presents more effective cell permeation. Effective and selective cytotoxicity toward the malignant cells, as compared to nonmalignant epithelial MCF-10A breast cells, is demonstrated due to the acidic pH, present in cancer cells, or the miRNA-21, present in MDA-MB-231 malignant cells.
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http://dx.doi.org/10.1021/acsnano.0c09996DOI Listing
April 2021

Responsive optical probes for deep-tissue imaging: Photoacoustics and second near-infrared fluorescence.

Adv Drug Deliv Rev 2021 06 25;173:141-163. Epub 2021 Mar 25.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

Optical imaging has played a vital role in development of biomedicine and image-guided theragnostic. Nevertheless, the clinical translation of optical molecular imaging for deep-tissue visualization is still limited by poor signal-to-background ratio and low penetration depth owing to light scattering and tissue autofluorescence. Hence, to facilitate precise diagnosis and accurate surgery excision in clinical practices, the responsive optical probes (ROPs) are broadly designed for specific reaction with biological analytes or disease biomarkers via chemical/physical interactions for photoacoustic and second near-infrared fluorescence (NIR-II, 900-1700 nm) fluorescence imaging. Herein, the recent advances in the development of ROPs including molecular design principles, activated mechanisms and treatment responses for photoacoustic and NIR-II fluorescence imaging are reviewed. Furthermore, the present challenges and future perspectives of ROPs for deep-tissue imaging are also discussed.
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http://dx.doi.org/10.1016/j.addr.2021.03.008DOI Listing
June 2021

Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations.

Adv Mater 2021 Apr 17;33(16):e2100098. Epub 2021 Mar 17.

Department of Chemistry, Tsinghua University, Beijing, 100084, China.

As a typical inflammatory disease with chronic pain syndromes, rheumatoid arthritis (RA) generally requires long-term treatment with frequent injection administration at 1-2 times per day, because common medications such as interleukin1 receptor antagonist (IL1ra) have poor bioavailability and very limited half-life residence. Here a novel strategy to fabricate nanotherapeutic formulations employing genetically engineered IL1ra protein complexes, yielding ultralong-lasting bioefficacy is developed rationally. Using rat models, it is shown that these nanotherapeutics significantly improved drug regimen to a single subcutaneous administration in a 14-day therapy, suggesting their extraordinary bioavailability and ultralong-acting pharmacokinetics. Specifically, the half-life and bioavailability of the nanoformulations are boosted to the level of 30 h and by 7 times, respectively, significantly greater than other systems. This new strategy thus holds great promise to potently improve patient compliance in RA therapy, and it can be adapted for other therapies that suffer similar drawbacks.
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http://dx.doi.org/10.1002/adma.202100098DOI Listing
April 2021

DNA nanotechnology-empowered nanoscopic imaging of biomolecules.

Chem Soc Rev 2021 May 17;50(9):5650-5667. Epub 2021 Mar 17.

Institute of Molecular Medicine, Department of Urology, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Advances in bioimaging technologies have led to unprecedented findings of novel biological processes at the nanoscale. However, there remains an ever-lasting demand for the improvement of spatiotemporal resolution, multiplexity, and smart responsiveness of bioimaging in living systems. In recent decades, self-assembled DNA nanostructures with highly programmable shape, nanometer addressability, and structural responsiveness have shown great promise in developing nanoscale probes and labels for high-performance bioimaging. Here, we briefly review the recent progress in structural DNA nanotechnology and the development of DNA frameworks, and summarize the bioimaging strategies empowered by DNA nanotechnology. We highlight the advantages of DNA nanostructures in overcoming the bottlenecks in bioimaging and discuss the challenges and opportunities in this field.
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http://dx.doi.org/10.1039/d0cs01281eDOI Listing
May 2021
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