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CCS Chemistry 2024年第3期6卷 719-732页

作者： Lele Sun Fengyun Shen Zijian Xiong Yu Chao chunhai fan Zhuang Liu Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Lab Carbon Based Functional Materials and DevicesSoochow UniversitySuzhou 215123Jiangsu School of Life Sciences Shanghai UniversityShanghai 200444 School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 201240

The spatial arrangement of activating ligands is known to have great influence on T cell activation.However,independently studying each ligand’s spatial organization parameter that affects T cell activation remains a great challenge.Here,with DNA origami,we precisely organized the CD3ɛantibodies simulating T cell receptor(TCR)ligands and CD28 antibodies simulating co-stimulatory ligands to interrogate the independent role of TCR-ligand spacing and local copy numbers as well as the spacing between TCR ligands and co-stimulatory ligands on T cell activation.We found that T cell activation benefited fromlocally concentrated TCR ligands with a shorter spacing and was maximized by an∼38 nm spacing between TCR ligands and co-stimulatory ligands.The T cell expander constructed based on our findings could efficiently expand CD8+T cells for tumor immunotherapy.Thus,the DNA nanostructurebased ligands’precise arrangement can be a unique tool in studying immune cell activations and cellbased immunotherapies.

关键词： DNA origami T cell activation T cell receptor immune cancer immunotherapy

Size-dependent cellular uptake and sustained drug release of PLGA particles

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Particuology 2023年第2期73卷 1-7页

作者： Rui Sun Xia Liu Yu Zhang Qian Li Ying Zhu chunhai fan Division of Physical Biology CAS Key Laboratory of Interfacial Physics and TechnologyShanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201800China The Interdisciplinary Research Center Shanghai Synchrotron Radiation FacilityZhangjiang LaboratoryShanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China

Poly(lactic-co-glycolic)acid(PLGA)particles have become a commonly used drug delivery strategy in the pharmaceutical industry.In this work,we aim to investigate the size-dependent cellular internalization of PLGA particles and its effects on sustained drug release.We prepared three different-sized particles using PLGA(200,500 and 2000 nm)ranging from submicrometer to micrometer.Dexamethasone(DEX)with excellent anti-inflammatory properties was used as a model drug to prepare DEX-loaded PLGA particles(DPs).We comprehensively investigated the encapsulation efficiency,cellular uptake and in vitro drug release profile.Pharmacodynamic assessment revealed that,in the lipopolysaccharide(LPS)-induced RAW 264.7 cells model,500 nm DPs showed sustained anti-inflammatory efficacy.This work provides important information for designing PLGA-based drug delivery systems for biomedical applications.

关键词： DEX-loaded PLGA particles(DPs) Sustained release Anti-inflammatory efficacy

Computer vision-aided bioprinting for bone research

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Bone Research 2022年第2期10卷 213-226页

作者： Changxi Liu Liqiang Wang Weijie Lu Jia Liu Chengliang Yang chunhai fan Qian Li Yujin Tang State Key Laboratory of Metal Matrix Composites School of Material Science and EngineeringShanghai Jiao Tong UniversityNo.800 Dongchuan RoadShanghai 200240China Affiliated Hospital of Youjiang Medical University for NationalitiesBaiseGuangxi 533000China School of Chemistry and Chemical Engineering National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China

Bioprinting is an emerging additive manufacturing technology that has enormous potential in bone implantation and repair. The insufficient accuracy of the shape of bioprinted parts is a primary clinical barrier that prevents widespread utilization of bioprinting,especially for bone design with high-resolution requirements. During the last five years, the use of computer vision for process control has been widely practiced in the manufacturing field. Computer vision can improve the performance of bioprinting for bone research with respect to various aspects, including accuracy, resolution, and cell survival rate. Hence, computer vision plays a substantial role in addressing the current defect problem in bioprinting for bone research. In this review, recent advances in the application of computer vision in bioprinting for bone research are summarized and categorized into three groups based on different defect types: bone scaffold process control, deep learning, and cell viability models. The collection of printing parameters,data processing, and feedback of bioprinting information, which ultimately improves printing capabilities, are further discussed. We envision that computer vision may offer opportunities to accelerate bioprinting development and provide a new perception for bone research.

关键词： printing defect implantation

Probing the growth and mechanical properties of Bacillus subtilis biofilms through genetic mutation strategies

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Synthetic and Systems Biotechnology 2022年第3期7卷 965-971页

作者： Suying Liu Jiaofang Huang Chen Zhang Lihua Wang chunhai fan Chao Zhong Division of Physical Biology and Bioimaging Center Shanghai Institute of Applied PhysicsChinese Academy of SciencesShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Physical Science and Technology ShanghaiTech UniversityShanghaiChina State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghaiChina Institute of Physics Swiss Federal Institute of Technology Lausanne(EPFL)LausanneSwitzerland The Interdisciplinary Research Center Shanghai Advanced Research InstituteChinese Academy of SciencesZhangjiang LaboratoryShanghaiChina School of Chemistry and Chemical Engineering Institute of Molecular MedicineRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Center for Materials Synthetic Biology Shenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina

Bacterial communities form biofilms on various surfaces by synthesizing a cohesive and protective extracellular matrix,and these biofilms protect microorganisms against harsh environmental conditions.Bacillus subtilis is a widely used experimental species,and its biofilms are used as representative models of beneficial biofilms.Specifically,B.subtilis biofilms are known to be rich in extracellular polymeric substances(EPS)and other biopolymers such as DNA and proteins like the amyloid protein TasA and the hydrophobic protein BslA.These materials,which form an interconnected,cohesive,three-dimensional polymer network,provide the mechanical stability of biofilms and mediate their adherence to surfaces among other functional contributions.Here,we explored how genetically-encoded components specifically contribute to regulate the growth status,mechanical properties,and antibiotic resistance of B.subtilis biofilms,thereby establishing a solid empirical basis for understanding how various genetic engineering efforts are likely to affect the structure and function of biofilms.We noted discrete contributions to biofilm morphology,mechanical properties,and survival from major biofilm components such as EPS,TasA and BslA.For example,EPS plays an important role in maintaining the stability of the mechanical properties and the antibiotic resistance of biofilms,whereas BslA has a significant impact on the resolution that can be obtained for printing applications.This work provides a deeper understanding of the internal interactions of biofilm components through systematic genetic manipulations.It thus not only broadens the application prospects of beneficial biofilms,but also serves as the basis of future strategies for targeting and effectively removing harmful biofilms.

关键词： Bacillus subtilis Biofilms Synthetic biology Living materials Environmental tolerance

Pharmaceutical applications of framework nucleic acids

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Acta Pharmaceutica Sinica B 2022年第1期12卷 76-91页

作者： Liang Chen Jie Zhang Zhun Lin Ziyan Zhang Miao Mao Jiacheng Wu Qian Li Yuanqing Zhang chunhai fan School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acids Chemistry and NanomedicineRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids(FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.

关键词： DNA nanotechnology Self-assembly Framework nucleic acids DNA nanostructures Drug discovery Therapeutic molecules Drug delivery Drug analysis

DNA Nanostructure-Guided Plasmon Coupling Architectures

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CCS Chemistry 2023年第3期5卷 568-588页

作者： Mengmeng Liu Xiaoyu Zhang Lulu Huang Jie Li chunhai fan Yang Tian Shanghai Key Laboratory of Green Chemistry and Chemical Processes School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241 School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative MoleculesInstitute of Translational MedicineShanghai Jiao Tong UniversityShanghai 200240

Plasmon coupling architectures with specific spatial and orientational arrangement configurations possess unique and tailored plasmonic properties and hold promise for advancements in nano-optics,nanoantennas,and biosensors.Numerous research has focused on the construction of plasmonic assemblies with predetermined configurations.DNA nanostructures with arbitrary geometry,high compatibility with metal nanoparticles,and spatial addressability meet the requirement for precise spatial and orientation arrangement.Currently,DNA nanostructures are widely exploited as structural materials to generate plasmonic structures with well-defined topologies.We review the evolution of DNA nanostructureguided plasmon coupling architectures,including the introduction of DNA nanostructures,DNA modification on the surface of plasmonic nanoparticles,and three strategies for constructing complex plasmonic nanostructures.Then we focus on the emerging applications of DNA nanostructure-guided architectures with engineered local electromagnetic enhancement for modulating plasmon coupling,amplifying emitter signals,and serving as biosensors.Finally,we will critically discuss the challenges and opportunities in this field.

关键词： DNA nanostructures plasmonic nanoparticles localized surface plasmon resonance plasmon coupling architectures

ssDNA functionalized nanodiamonds for uranium decorporation

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Chinese Chemical Letters 2022年第7期33卷 3570-3572页

作者： Qinglong Yan Yu Miao Xiaomei Wang Jifei Ma Juan Diwu Ying Zhu Shuao Wang chunhai fan Interdisciplinary Research Center Shanghai Synchrotron Radiation FacilityZhangjiang LaboratoryShanghai Advanced Research InstituteChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 201210China Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences(RAD-X)and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou 215123China School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China

The hunt for agents that are suitable for actinide decorporation to reduce the whole-body load of actinide in accidental internal exposure is the ever-lasting goal in radiation protection and medical treatment in nuclear emergency.All current decorporation agents can be categorized as two groups,one is the molecular ligands,and the other is the nanoparticles decorated with molecular ligands.Here in this work,functional nanodiamonds(fN Ds)with ss DNA(the endogenous biomacromolecule rich in phosphate groups)loaded on the NDs is reported,which poses good uranyl adsorption selectivity,high cellular uptake,fast excretion,and effective decorporation of uranyl from rat renal proximal tubular epithelial cells(NRK-52E).All those results corroborate that f NDs can potentially serve as a brand new family of chelators for actinide decorporation.

关键词： Nanodiamond ssDNA Uranium Decorporation

DNA framework-engineered electrochemical biosensors

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Science China(Life Sciences) 2020年第8期63卷 1130-1141页

作者： fan Li Qian Li Xiaolei Zuo chunhai fan Institute of Molecular Medicine Renji HospitalSchools of MedicineShanghai Jiao Tong UniversityShanghai 200127China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Self-assembled DNA nanostructures have shown remarkable potential in the engineering of biosensing interfaces,which can improve the performance of various biosensors.In particular,by exploiting the structural rigidity and programmability of the framework nucleic acids with high precision,molecular recognition on the electrochemical biosensing interface has been significantly enhanced,leading to the development of highly sensitive and specific biosensors for nucleic acids,small molecules,proteins,and cells.In this review,we summarize recent advances in DNA framework-engineered biosensing interfaces and the application of corresponding electrochemical biosensors.

关键词： framework nucleic acids biosensing interface electrochemical biosensors biomarkers DNA

Advancing pathogen detection for airborne diseases

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Fundamental Research 2023年第4期3卷 520-524页

作者： Tingting Zhai Yuhan Wei Lihua Wang Jiang Li chunhai fan School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China Institute of Materiobiology Department of ChemistryCollege of ScienceShanghai UniversityShanghai 200444China The Interdisciplinary Research Center Shanghai Synchrotron Radiation FacilityZhangjiang LaboratoryShanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China

Airborne diseases including SARS,bird flu,and the ongoing Coronavirus Disease 2019(COVID-19)have stimulated the demand for developing novel bioassay methods competent for early-stage diagnosis and large-scale screening.Here,we briefly summarize the state-of-the-art methods for the detection of infectious pathogens and discuss key challenges.We highlight the trend for next-generation technologies benefiting from multidisciplinary advances in microfabrication,nanotechnology and synthetic biology,which allow sensitive,rapid yet inexpensive pathogen assays with portable intelligent device.

关键词： Infectious disease Pathogen assay Biosensor Synthetic biological circuit Smart device

Highly reliable and efficient encoding systems for hexadecimal polypeptide-based data storage

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Fundamental Research 2023年第2期3卷 298-304页

作者： Yubin Ren Yi Zhang Yawei Liu Qinglin Wu Hong-Gang Hu Jingjing Li chunhai fan Dong Chen Kai Liu Hongjie Zhang Department of Chemistry Tsinghua UniversityBeijing 100084China State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Institute of Process Equipment College of Energy Engineering and State Key Laboratory of Fluid Power and Mechatronic SystemsZhejiang UniversityHangzhou 310027China Institute of Translational Medicine Shanghai UniversityShanghai 200444China Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical Engineeringand Institute of Molecular MedicineRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China

Polypeptides consisting of amino acid(AA)sequences are suitable for high-density information storage.However,the lack of suitable encoding systems,which accommodate the characteristics of polypeptide synthesis,storage and sequencing,impedes the application of polypeptides for large-scale digital data storage.To address this,two reliable and highly efficient encoding systems,i.e.RaptorQ-Arithmetic-Base64-Shuffle-RS(RABSR)and RaptorQArithmetic-Huffman-Rotary-Shuffle-RS(RAHRSR)systems,are developed for polypeptide data storage.The two encoding systems realized the advantages of compressing data,correcting errors of AA chain loss,correcting errors within AA chains,eliminating homopolymers,and pseudo-randomized encrypting.The coding efficiency without arithmetic compression and error correction of audios,pictures and texts by the RABSR system was 3.20,3.12 and 3.53 Bits/AA,respectively.While that using the RAHRSR system reached 4.89,4.80 and 6.84 Bits/AA,respectively.When implemented with redundancy for error correction and arithmetic compression to reduce redundancy,the coding efficiency of audios,pictures and texts by the RABSR system was 4.43,4.36 and 5.22 Bits/AA,respectively.This efficiency further increased to 7.24,7.11 and 9.82 Bits/AA by the RAHRSR system,respectively.Therefore,the developed hexadecimal polypeptide-based systems may provide a new scenario for highly reliable and highly efficient data storage.

关键词： Biomaterial Polypeptide Data storage Hexadecimal Encoding system