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1
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Mirkin CA, Langer R, Mrksich M, Margolin AA, Petrosko SH, Artzi N. Blueprints for Better Drugs: The Structural Revolution in Nanomedicine. ACS NANO 2025. [PMID: 40359339 DOI: 10.1021/acsnano.5c06380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
Structural nanomedicines are engineered constructs that arrange therapeutic components into well-defined architectures to maximize efficacy. Their multivalent, multifunctional design offers key advantages over unstructured formulations, including targeted delivery, expanded therapeutic windows, and enhanced target engagement. The mRNA COVID-19 vaccines exemplify their transformative potential. However, structural precision varies, and more well-defined architectures will streamline optimization, manufacturing, and regulation. Unlike small molecule drugs, nanomedicines within a batch are not identical. Identifying the most effective, least toxic structures will advance our understanding of structure-function relationships and therapeutic mechanisms. This work highlights structural nanomedicines─small molecules, nucleic acids, and biologics─to galvanize the field and drive innovation toward even safer, more effective treatments that benefit patients.
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Affiliation(s)
- Chad A Mirkin
- Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
- International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States
- Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, United States
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States
- CZ Biohub Chicago, LLC, Chicago, Illinois 60642, United States
| | - Robert Langer
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Milan Mrksich
- Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
- International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States
- Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, United States
- Department of Cellular and Developmental Biology, Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60208, United States
| | - Adam A Margolin
- Flashpoint Therapeutics, Evanston, Illinois 60201, United States
| | - Sarah Hurst Petrosko
- Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States
- International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States
| | - Natalie Artzi
- Brigham and Women's Hospital, Department of Medicine, Division of Engineering in Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts 02215, United States
- Institute for Biomedical Engineering and Science, Biomedical Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02115, United States
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02215, United States
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2
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Sheu KM, Hoffmann A. Protocol for the imputation of stimulus-induced single-cell gene expression trajectories from time-series scRNA-seq data. STAR Protoc 2025; 6:103811. [PMID: 40343799 DOI: 10.1016/j.xpro.2025.103811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 03/08/2025] [Accepted: 04/16/2025] [Indexed: 05/11/2025] Open
Abstract
Single-cell RNA sequencing (scRNA-seq) measures cell-to-cell heterogeneous mRNA abundance but destroys the cell and precludes tracking of heterogeneous gene expression trajectories. Here, we present an approach to impute single-cell gene expression trajectories (scGETs) from time-series scRNA-seq measurements. We describe four main computational steps: dimensionality reduction, calculation of transition probability matrices, spline interpolation, and deconvolution to scGETs. Imputing scGETs can aid in studying heterogeneous stimulus responses over time, such as cancer cell responses to drugs or immune cell responses to pathogens. For complete details on the use and execution of this protocol, please refer to Sheu et al.1.
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Affiliation(s)
- Katherine M Sheu
- Department of Microbiology, Immunology, and Molecular Genetics, Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, 611 Charles E. Young Dr E, Los Angeles, CA 90095, USA.
| | - Alexander Hoffmann
- Department of Microbiology, Immunology, and Molecular Genetics, Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, 611 Charles E. Young Dr E, Los Angeles, CA 90095, USA.
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3
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Ren L, Cao S, Guo L, Li J, Jiao K, Wang L. Recent advances in nucleic acid-functionalized metallic nanoparticles. Chem Commun (Camb) 2025; 61:4904-4923. [PMID: 40047804 DOI: 10.1039/d5cc00359h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
Nucleic acid-functionalized metallic nanoparticles (N-MNPs) precisely integrate the advantageous characteristics of nucleic acids and metallic nanomaterials, offering various abilities such as resistance to enzymatic degradation, penetration of physiological barriers, controllable mobility, biomolecular recognition, programmable self-assembly, and dynamic structure-function transformation. These properties demonstrate significant potential in the field of biomedical diagnostics and therapeutics. In this review, we examine recent advancements in the construction and theranostic applications of N-MNPs. We briefly summarize the methodologies employed in the conjugation of nucleic acids with metallic nanoparticles and the formation of their superstructural assemblies. We highlight recent representative applications of N-MNPs in biomolecular diagnosis, imaging, and smart delivery of theranostic agents. We also discuss challenges currently faced in this field and provide an outlook on future development directions and application prospects.
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Affiliation(s)
- Lei Ren
- Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
- University of Chinese Academy of Sciences, Beijing 100049, China
- Institute of Materiobiology, College of Sciences, Shanghai University, Shanghai 200444, China.
| | - Shuting Cao
- Jiaxing Key Laboratory of Biosemiconductors, Xiangfu Laboratory, Jiashan 314102, Zhejiang, China
- Nano-translational Medicine Research Center, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing 314000, China
| | - Linjie Guo
- Institute of Materiobiology, College of Sciences, Shanghai University, Shanghai 200444, China.
| | - Jiang Li
- Institute of Materiobiology, College of Sciences, Shanghai University, Shanghai 200444, China.
| | - Kai Jiao
- Institute of Materiobiology, College of Sciences, Shanghai University, Shanghai 200444, China.
| | - Lihua Wang
- Institute of Materiobiology, College of Sciences, Shanghai University, Shanghai 200444, China.
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4
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Dai K, Zhao J, Li L, Fu X. Spatially Controlled MicroRNA Imaging in Mitochondria via Enzymatic Activation of Hybridization Chain Reaction. SMALL METHODS 2024:e2401531. [PMID: 39543789 DOI: 10.1002/smtd.202401531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 11/03/2024] [Indexed: 11/17/2024]
Abstract
Live-cell imaging of RNA in specific subcellular compartments is essential for elucidating the rich repertoire of cellular functions, but it has been limited by a lack of simple, precisely controlled methods. Here such an approach is presented via the combination of hybridization chain reaction and spatially restricted enzymatic activation with organelle-targeted delivery. The system can localize engineered DNA hairpins in the mitochondria, where target RNA-initiated chain reaction of hybridization events is selectively activated by a specific enzyme, enabling amplified RNA imaging with high precision. It is demonstrated that the approach is compatible with live cell visualization and enables the regulatable imaging of microRNA in mitochondria. Since in situ activation of the signal amplification with enzyme eliminates the need for genetically encoded protein overexpression, it is envisioned that this simple platform will be broadly applicable for precise RNA imaging with subcellular resolution in a variety of biological processes.
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Affiliation(s)
- Kaining Dai
- Sanbo Brain Hospital, Capital Medical University, Laboratory for Clinical Medicine, Capital Medical University, Beijing, 100070, China
| | - Jian Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Lele Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Xiaojun Fu
- Sanbo Brain Hospital, Capital Medical University, Laboratory for Clinical Medicine, Capital Medical University, Beijing, 100070, China
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5
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Liu W, Chung K, Yu S, Lee LP. Nanoplasmonic biosensors for environmental sustainability and human health. Chem Soc Rev 2024; 53:10491-10522. [PMID: 39192761 DOI: 10.1039/d3cs00941f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
Monitoring the health conditions of the environment and humans is essential for ensuring human well-being, promoting global health, and achieving sustainability. Innovative biosensors are crucial in accurately monitoring health conditions, uncovering the hidden connections between the environment and human well-being, and understanding how environmental factors trigger autoimmune diseases, neurodegenerative diseases, and infectious diseases. This review evaluates the use of nanoplasmonic biosensors that can monitor environmental health and human diseases according to target analytes of different sizes and scales, providing valuable insights for preventive medicine. We begin by explaining the fundamental principles and mechanisms of nanoplasmonic biosensors. We investigate the potential of nanoplasmonic techniques for detecting various biological molecules, extracellular vesicles (EVs), pathogens, and cells. We also explore the possibility of wearable nanoplasmonic biosensors to monitor the physiological network and healthy connectivity of humans, animals, plants, and organisms. This review will guide the design of next-generation nanoplasmonic biosensors to advance sustainable global healthcare for humans, the environment, and the planet.
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Affiliation(s)
- Wenpeng Liu
- Department of Medicine, Brigham Women's Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA.
| | - Kyungwha Chung
- Department of Medicine, Brigham Women's Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA.
- Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Subin Yu
- Department of Medicine, Brigham Women's Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA.
| | - Luke P Lee
- Department of Medicine, Brigham Women's Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA.
- Department of Bioengineering, Department of Electrical Engineering and Computer Science, University of California at Berkeley, Berkeley, CA 94720, USA
- Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Republic of Korea
- Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Korea
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Tang X, Zhao S, Luo J, Wang B, Wu X, Deng R, Chang K, Chen M. Smart Stimuli-Responsive Spherical Nucleic Acids: Cutting-Edge Platforms for Biosensing, Bioimaging, and Therapeutics. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2310732. [PMID: 38299771 DOI: 10.1002/smll.202310732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/27/2023] [Indexed: 02/02/2024]
Abstract
Spherical nucleic acids (SNAs) with exceptional colloidal stability, multiple modularity, and programmability are excellent candidates to address common molecular delivery-related issues. Based on this, the higher targeting accuracy and enhanced controllability of stimuli-responsive SNAs render them precise nanoplatforms with inestimable prospects for diverse biomedical applications. Therefore, tailored diagnosis and treatment with stimuli-responsive SNAs may be a robust strategy to break through the bottlenecks associated with traditional nanocarriers. Various stimuli-responsive SNAs are engineered through the incorporation of multifunctional modifications to meet biomedical demands with the development of nucleic acid functionalization. This review provides a comprehensive overview of prominent research in this area and recent advancements in the utilization of stimuli-responsive SNAs in biosensing, bioimaging, and therapeutics. For each aspect, SNA nanoplatforms that exhibit responsive behavior to both internal stimuli (including sequence, enzyme, redox reactions, and pH) and external stimuli (such as light and temperature) are highlighted. This review is expected to offer inspiration and guidance strategies for the rational design and development of stimuli-responsive SNAs in the field of biomedicine.
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Affiliation(s)
- Xiaoqi Tang
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
| | - Shuang Zhao
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
| | - Jie Luo
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
| | - Binpan Wang
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
| | - Xianlan Wu
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
| | - Ruijia Deng
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
| | - Kai Chang
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
| | - Ming Chen
- Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
- College of Pharmacy and Laboratory Medicine, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China
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7
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Liu S, Yu CY, Wei H. Spherical nucleic acids-based nanoplatforms for tumor precision medicine and immunotherapy. Mater Today Bio 2023; 22:100750. [PMID: 37545568 PMCID: PMC10400933 DOI: 10.1016/j.mtbio.2023.100750] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 07/23/2023] [Accepted: 07/26/2023] [Indexed: 08/08/2023] Open
Abstract
Precise diagnosis and treatment of tumors currently still face considerable challenges due to the development of highly degreed heterogeneity in the dynamic evolution of tumors. With the rapid development of genomics, personalized diagnosis and treatment using specific genes may be a robust strategy to break through the bottleneck of traditional tumor treatment. Nevertheless, efficient in vivo gene delivery has been frequently hampered by the inherent defects of vectors and various biological barriers. Encouragingly, spherical nucleic acids (SNAs) with good modularity and programmability are excellent candidates capable of addressing traditional gene transfer-associated issues, which enables SNAs a precision nanoplatform with great potential for diverse biomedical applications. In this regard, there have been detailed reviews of SNA in drug delivery, gene regulation, and dermatology treatment. Still, to the best of our knowledge, there is no published systematic review summarizing the use of SNAs in oncology precision medicine and immunotherapy, which are considered new guidelines for oncology treatment. To this end, we summarized the notable advances in SNAs-based precision therapy and immunotherapy for tumors following a classification standard of different types of precise spatiotemporal control on active species by SNAs. Specifically, we focus on the structural diversity and programmability of SNAs. Finally, the challenges and possible solutions were discussed in the concluding remarks. This review will promote the rational design and development of SNAs for tumor-precise medicine and immunotherapy.
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Affiliation(s)
- Songbin Liu
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Cui-Yun Yu
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Hua Wei
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, China
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8
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Mirkin CA, Petrosko SH. Inspired Beyond Nature: Three Decades of Spherical Nucleic Acids and Colloidal Crystal Engineering with DNA. ACS NANO 2023; 17:16291-16307. [PMID: 37584399 DOI: 10.1021/acsnano.3c06564] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/17/2023]
Abstract
The conception, synthesis, and invention of a nanostructure, now known as the spherical nucleic acid, or SNA, in 1996 marked the advent of a new field of chemistry. Over the past three decades, the SNA and its analogous anisotropic equivalents have provided an avenue for us to think about some of the most fundamental concepts in chemistry in new ways and led to technologies that are significantly impacting fields from medicine to materials science. A prime example is colloidal crystal engineering with DNA, the framework for using SNAs and related structures to synthesize programmable matter. Herein, we document the evolution of this framework, which was initially inspired by nature, and describe how it now allows researchers to chart paths to move beyond it, as programmable matter with real-world significance is envisioned and created.
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Affiliation(s)
- Chad A Mirkin
- Department of Chemistry and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States
| | - Sarah Hurst Petrosko
- Department of Chemistry and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States
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9
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Karami A, Hasani M. Methods to functionalize gold nanoparticles with tandem-phosphorothioate DNA: role of physicochemical properties of the phosphorothioate backbone in DNA adsorption to gold nanoparticles. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2023; 15:4104-4113. [PMID: 37551768 DOI: 10.1039/d3ay00960b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/09/2023]
Abstract
Perception of the differences in the physicochemical properties of phosphorothioate DNA (PS-DNA) and phosphodiester DNA (PO-DNA) greatly aids in understanding the AuNP-DNA binding process. Replacing one non-bridging oxygen atom of the anionic phosphodiester backbone with a sulfur atom leads to a major change in the DNA adsorption mechanism of AuNPs. In this work, we investigated and compared salt-aging, low pH-assisted, and freeze-thaw methods for conjugating phosphorothioate-modified oligonucleotides to AuNPs. The results obtained clearly demonstrate that only the pH-assisted method can successfully bind tandem phosphorothioate DNA to gold nanoparticles and sufficiently maintain the colloidal stability of AuNPs. When a phosphate group is converted to a phosphorothioate group, the negative charge of the phosphate group is located on the sulfur atom. Due to the soft nature of sulfur (a very weak H-bond acceptor), the negative charge on the sulfur atom cannot be shielded even with the gradual addition of salt to increase the ionic strength, so, the pH-assisted based method is the best for the functionalization of AuNPs with tandem-PS DNA.
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Affiliation(s)
- Abbas Karami
- Faculty of Chemistry, Bu-Ali Sina University, Hamedan 65174, Iran.
| | - Masoumeh Hasani
- Faculty of Chemistry, Bu-Ali Sina University, Hamedan 65174, Iran.
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10
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Akiyama Y, Kimura K, Komatsu S, Takarada T, Maeda M, Kikuchi A. A Simple Colorimetric Assay of Bleomycin-Mediated DNA Cleavage Utilizing Double-Stranded DNA-Modified Gold Nanoparticles. Chembiochem 2023; 24:e202200451. [PMID: 36156837 PMCID: PMC10092608 DOI: 10.1002/cbic.202200451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/23/2022] [Indexed: 01/05/2023]
Abstract
A colorimetric assay of DNA cleavage by bleomycin (BLM) derivatives was developed utilizing high colloidal stability on double-stranded (ds) DNA-modified gold nanoparticles (dsDNA-AuNPs) possessing a cleavage site. The assay was performed using dsDNA-AuNPs treated with inactive BLM or activated BLM (Fe(II)⋅BLM). A 10-min exposure in dsDNA-AuNPs with inactive BLM treatment resulted in a rapid color change from red to purple because of salt-induced non-crosslinking aggregation of dsDNA-AuNPs. In contrast, the addition of active Fe(II)⋅BLM retained the red color, probably because of the formation of protruding structures at the outermost phase of dsDNA-AuNPs caused by BLM-mediated DNA cleavage. Furthermore, the results of our model experiments indicate that oxidative base release and DNA-cleavage pathways could be visually distinguished with color change. The present methodology was also applicable to model screening assays using several drugs with different mechanisms related to antitumor activity. These results strongly suggest that this assay with a rapid color change could lead to simple and efficient screening of potent antitumor agents.
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Affiliation(s)
- Yoshitsugu Akiyama
- Katsushika Division, Institute of Arts and Sciences, Tokyo University of Science, 6-3-1 Niijuku, 125-8585, Katsushika, Tokyo, Japan.,Department of Materials Science and Technology, Graduate School of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, 125-8585, Katsushika, Tokyo, Japan
| | - Kazunori Kimura
- Department of Materials Science and Technology, Graduate School of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, 125-8585, Katsushika, Tokyo, Japan
| | - Syuuhei Komatsu
- Department of Materials Science and Technology, Graduate School of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, 125-8585, Katsushika, Tokyo, Japan
| | - Tohru Takarada
- Surface and Interface Science Laboratory, RIKEN, 2-1 Hirosawa, 351-0198, Wako, Saitama, Japan
| | - Mizuo Maeda
- RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, 351-0198, Wako, Saitama, Japan
| | - Akihiko Kikuchi
- Department of Materials Science and Technology, Graduate School of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, 125-8585, Katsushika, Tokyo, Japan
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11
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Liu X, Yang Q, Sui Y, Yue Q, Yan S, Li C, Hong M. Monitoring and Regulating Intracellular GPX4 mRNA Using Gold Nanoflare Probes and Enhancing Erastin-Induced Ferroptosis. BIOSENSORS 2022; 12:1178. [PMID: 36551145 PMCID: PMC9776005 DOI: 10.3390/bios12121178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/02/2022] [Accepted: 12/14/2022] [Indexed: 06/17/2023]
Abstract
Glutathione peroxidase 4 (GPX4) plays an important effect on ferroptosis. Down-regulating the expression of GPX4 mRNA can decrease the content of GPX4. In this work, a gold nanoflare (AuNF) probe loaded with anti-sense sequences targeting for GPX4 mRNA was designed to monitor and down-regulate intracellular GPX4 mRNA using fluorescence imaging in situ and using anti-sense technology. The results revealed that there was a marked difference for the expression of GPX4 mRNA in different cell lines, and the survival rate of cancer cells was not significantly effected when the relative mRNA and protein expression levels of GPX4 was down-regulated by AuNF probes. However, when co-treated with AuNF probes, the low expression of GPX4 strengthened erastin-induced ferroptosis, and this synergy showed a better effect on inhibiting the proliferation of cancer cells.
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Affiliation(s)
- Xiaoyan Liu
- School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
| | - Qiangqiang Yang
- School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
| | - Yanan Sui
- School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
| | - Qiaoli Yue
- School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
| | - Shuqing Yan
- School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
| | - Chuan Li
- School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
| | - Min Hong
- School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
- Shandong Harway Pharma Co., Ltd., Dongying 257000, China
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12
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Dong F, Yan W, Dong W, Shang X, Xu Y, Liu W, Wu Y, Wei W, Zhao T. DNA-enabled fluorescent-based nanosensors monitoring tumor-related RNA toward advanced cancer diagnosis: A review. Front Bioeng Biotechnol 2022; 10:1059845. [DOI: 10.3389/fbioe.2022.1059845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 11/18/2022] [Indexed: 12/02/2022] Open
Abstract
As a burgeoning non-invasive indicator for reproducible cancer diagnosis, tumor-related biomarkers have a wide range of applications in early cancer screening, efficacy monitoring, and prognosis predicting. Accurate and efficient biomarker determination, therefore, is of great importance to prevent cancer progression at an early stage, thus reducing the disease burden on the entire population, and facilitating advanced therapies for cancer. During the last few years, various DNA structure-based fluorescent probes have established a versatile platform for biological measurements, due to their inherent biocompatibility, excellent capacity to recognize nucleic and non-nucleic acid targets, obvious accessibility to synthesis as well as chemical modification, and the ease of interfacing with signal amplification protocols. After decades of research, DNA fluorescent probe technology for detecting tumor-related mRNAs has gradually grown to maturity, especially the advent of fluorescent nanoprobes has taken the process to a new level. Here, a systematic introduction to recent trends and advances focusing on various nanomaterials-related DNA fluorescent probes and the physicochemical properties of various involved nanomaterials (such as AuNP, GO, MnO2, SiO2, AuNR, etc.) are also presented in detail. Further, the strengths and weaknesses of existing probes were described and their progress in the detection of tumor-related mRNAs was illustrated. Also, the salient challenges were discussed later, with a few potential solutions.
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13
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Spherical nucleic acids-based biosensors for cancer biomarkers detection. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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14
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Pelea O, Fulga TA, Sauka-Spengler T. RNA-Responsive gRNAs for Controlling CRISPR Activity: Current Advances, Future Directions, and Potential Applications. CRISPR J 2022; 5:642-659. [PMID: 36206027 PMCID: PMC9618385 DOI: 10.1089/crispr.2022.0052] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 08/17/2022] [Indexed: 01/31/2023] Open
Abstract
CRISPR-Cas9 has emerged as a major genome manipulation tool. As Cas9 can cause off-target effects, several methods for controlling the expression of CRISPR systems were developed. Recent studies have shown that CRISPR activity could be controlled by sensing expression levels of endogenous transcripts. This is particularly interesting, as endogenous RNAs could harbor important information about the cell type, disease state, and environmental challenges cells are facing. Single-guide RNA (sgRNA) engineering played a major role in the development of RNA-responsive CRISPR systems. Following further optimizations, RNA-responsive sgRNAs could enable the development of novel therapeutic and research applications. This review introduces engineering strategies that could be employed to modify Streptococcus pyogenes sgRNAs with a focus on recent advances made toward the development of RNA-responsive sgRNAs. Future directions and potential applications of these technologies are also discussed.
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Affiliation(s)
- Oana Pelea
- Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom; and Kansas City, Missouri, USA
| | - Tudor A. Fulga
- Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom; and Kansas City, Missouri, USA
| | - Tatjana Sauka-Spengler
- Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom; and Kansas City, Missouri, USA
- Stowers Institute for Medical Research, Kansas City, Missouri, USA
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15
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Yang Y, Luo T, He Y, Deng Z, Li J, Liu H, Nie J, Wang D, Huang J, Zhong S. Nanoflare Couple: Multiplexed mRNA Imaging and Logic-Controlled Combinational Therapy. Anal Chem 2022; 94:12204-12212. [PMID: 36007146 DOI: 10.1021/acs.analchem.2c02689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Theranostics, which combines both diagnostic and therapeutic capabilities in one dose, has always been an intractable challenge in personalized cancer treatment. Herein, a versatile nanotheranostic platform "nanoflare couple (NC)" has been developed for in situ multiplex cancer-related mRNA imaging and subsequent logic-controlled aggregation of gold nanoparticles, leading to gene therapy and photothermal therapy upon irradiation with infrared light. As a proof of concept, TK1 and survivin mRNAs that are highly expressed in most tumor tissues are selected as endogenous cancer indicators and therapy triggers to design the NC. Mice bearing breast cancer cells MCF-7 are prepared as a model to test its efficacy. The in vitro and in vivo assays validate that the NC show the capability for multiplexed mRNA imaging and high efficiency for logic-controlled combinational therapy of breast cancer.
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Affiliation(s)
- Yanjing Yang
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Tong Luo
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Yao He
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Zhiwei Deng
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Jiacheng Li
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Hui Liu
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Jing Nie
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - De Wang
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Jin Huang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, P. R. China
| | - Shian Zhong
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
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16
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Zhao Y, Zhao J, Zhang J, Sun Y, Li L, Li Z, Li M. Enzymatically Controlled Nanoflares for Specific Molecular Recognition and Biosensing. Anal Chem 2022; 94:8883-8889. [PMID: 35704434 DOI: 10.1021/acs.analchem.2c00166] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In situ sensing of physiological and pathological species in cancer cells is of great importance to unravel their molecular and cellular processes. However, the biosensing with conventional probes is often limited by the undesired on-target off-tumor interference. Here, we report a novel strategy to design enzymatically controlled nanoflares for sensing and imaging molecular targets in tumor cells. The triggerable nanoflare was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on gold nanoparticles. The nanoflare sensors did not respond to target molecules in normal cells, but they could be catalytically activated by specific enzymes in cancer cells, thereby enabling cancer-specific sensing and imaging in vitro and in vivo with improved tumor specificity. Considering that diverse aptamers were selected, we expect that this strategy would facilitate the precise detection of a broad range of targets in tumors and may promote the development of smart probes for cancer diagnosis.
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Affiliation(s)
- Ya Zhao
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Jian Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Jingfang Zhang
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Yan Sun
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Lele Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China
| | - Zhengping Li
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Mengyuan Li
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
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17
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Li Z, Feng X, Hu W, Li L. An activatable DNA nanodevice for correlated imaging of apoptosis-related dual proteins. NANOSCALE 2022; 14:6465-6470. [PMID: 35416226 DOI: 10.1039/d2nr00537a] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Apoptosis plays an important role in the life cycle of multicellular organisms. The development of techniques for sensitive monitoring of apoptosis-related key molecules can be used to assess not only disease progression but also its therapeutic interventions. However, there is still a lack of an imaging probe amenable for simultaneously detecting multiple biomarkers during drug-induced apoptosis. Herein, a novel activatable DNA nanodevice was designed to image apoptosis-related dual proteins in real time. The turn-on and specific recognition properties of our probe allow the spatially selective detection of apoptotic-related marker cytochrome c and apurinic/apyrimidinic endonuclease 1 in living cells. We demonstrated that the DNA nanodevice has the ability to monitor apoptosis and evaluate the efficacy of apoptosis-related drugs, which potentially can be used as a tool to evaluate the molecular mechanism of apoptosis regulation or to screen apoptotic drugs.
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Affiliation(s)
- Zhixiang Li
- Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin 300072, China
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
| | - Xueyan Feng
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
| | - Wenping Hu
- Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin 300072, China
| | - Lele Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
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18
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Harbauer AB, Hees JT, Wanderoy S, Segura I, Gibbs W, Cheng Y, Ordonez M, Cai Z, Cartoni R, Ashrafi G, Wang C, Perocchi F, He Z, Schwarz TL. Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy. Neuron 2022; 110:1516-1531.e9. [PMID: 35216662 PMCID: PMC9081165 DOI: 10.1016/j.neuron.2022.01.035] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 06/25/2021] [Accepted: 01/28/2022] [Indexed: 01/18/2023]
Abstract
PTEN-induced kinase 1 (PINK1) is a short-lived protein required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane proteins synaptojanin 2 binding protein (SYNJ2BP) and synaptojanin 2 (SYNJ2) are required for tethering Pink1 mRNA to mitochondria via an RNA-binding domain in SYNJ2. This neuron-specific adaptation for the local translation of PINK1 provides distal mitochondria with a continuous supply of PINK1 for the activation of mitophagy.
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Affiliation(s)
- Angelika B Harbauer
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany; Institute of Neuronal Cell Biology, Technical University of Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster of Systems Neurology, Feodor-Lynen-Straße 17, 81377 Munich, Germany.
| | - J Tabitha Hees
- Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany
| | - Simone Wanderoy
- Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany
| | - Inmaculada Segura
- Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany; Ludwig-Maximilians-Universität München, Department of Cellular Physiology Biomedical Center Munich - BMC, Großhaderner Str. 9, 82152 Martinsried, Germany
| | - Whitney Gibbs
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
| | - Yiming Cheng
- Munich Cluster of Systems Neurology, Feodor-Lynen-Straße 17, 81377 Munich, Germany; Institute for Diabetes and Obesity, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Munich, Germany
| | - Martha Ordonez
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
| | - Zerong Cai
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
| | - Romain Cartoni
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
| | - Ghazaleh Ashrafi
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
| | - Chen Wang
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
| | - Fabiana Perocchi
- Institute of Neuronal Cell Biology, Technical University of Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster of Systems Neurology, Feodor-Lynen-Straße 17, 81377 Munich, Germany; Institute for Diabetes and Obesity, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Munich, Germany
| | - Zhigang He
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
| | - Thomas L Schwarz
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
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19
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Zhou H, Jiang Y, Zhao W, Zhang S. Light-Activated Nanodevice for On-Demand Imaging of miRNA in Living Cells via Logic Assembly. ACS APPLIED MATERIALS & INTERFACES 2022; 14:13070-13078. [PMID: 35258940 DOI: 10.1021/acsami.2c00376] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Low-abundance biomarker amplification detection systems have been widely used to detect miRNAs; however, "always active" systems are insufficient for high spatial and temporal control of miRNAs. Here, we constructed a light-activated nanodevice (LAN) based on DNA nanotechnology for high spatial and temporal precision detection of low-abundance miRNA. Light-activated hairpin probes and triple-helix molecular switches were modified on the surface of gold nanoparticles (AuNPs) to trigger miRNA on-demand imaging analysis by UV light activation. In the presence of both UV light and miRNA, the LAN releases hairpin DNA and completes the hybridization chain reaction (HCR) with the conformation-altered triple-helix molecular switch, enabling fluorescence imaging of low-abundance miRNAs in living cells. The current work provides an opportunity to develop light-activated signal amplification sensors that can accurately image miRNAs on-demand in both temporal and spatial dimensions.
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Affiliation(s)
- Huimin Zhou
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, Collaborative Innovation Center of Tumor Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, College of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, P. R. China
| | - Yao Jiang
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, Collaborative Innovation Center of Tumor Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, College of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, P. R. China
| | - Wenjing Zhao
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, Collaborative Innovation Center of Tumor Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, College of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, P. R. China
| | - Shusheng Zhang
- Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, Collaborative Innovation Center of Tumor Marker Detection Technology, Equipment and Diagnosis-Therapy Integration in Universities of Shandong, College of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, P. R. China
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20
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Cao H, Wang Y, Zhang N, Xia S, Tian P, Lu L, Du J, Du Y. Progress of CRISPR-Cas13 Mediated Live-Cell RNA Imaging and Detection of RNA-Protein Interactions. Front Cell Dev Biol 2022; 10:866820. [PMID: 35356276 PMCID: PMC8959342 DOI: 10.3389/fcell.2022.866820] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 02/21/2022] [Indexed: 12/26/2022] Open
Abstract
Ribonucleic acid (RNA) and proteins play critical roles in gene expression and regulation. The relevant study increases the understanding of various life processes and contributes to the diagnosis and treatment of different diseases. RNA imaging and mapping RNA-protein interactions expand the understanding of RNA biology. However, the existing methods have some limitations. Recently, precise RNA targeting of CRISPR-Cas13 in cells has been reported, which is considered a new promising platform for RNA imaging in living cells and recognition of RNA-protein interactions. In this review, we first described the current findings on Cas13. Furthermore, we introduced current tools of RNA real-time imaging and mapping RNA-protein interactions and highlighted the latest advances in Cas13-mediated tools. Finally, we discussed the advantages and disadvantages of Cas13-based methods, providing a set of new ideas for the optimization of Cas13-mediated methods.
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Affiliation(s)
- Huake Cao
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- First School of Clinical Medicine, Anhui Medical University, Hefei, China
| | - Yuechen Wang
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Second School of Clinical Medicine, Anhui Medical University, Hefei, China
| | - Ning Zhang
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- First School of Clinical Medicine, Anhui Medical University, Hefei, China
- First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Siyuan Xia
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- Second School of Clinical Medicine, Anhui Medical University, Hefei, China
| | - Pengfei Tian
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- First School of Clinical Medicine, Anhui Medical University, Hefei, China
- First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Li Lu
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Juan Du
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, China
- Longgang District People’s Hospital of Shenzhen & The Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen, China
- *Correspondence: Yinan Du, ; Juan Du,
| | - Yinan Du
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
- *Correspondence: Yinan Du, ; Juan Du,
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21
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Song Y, Song W, Lan X, Cai W, Jiang D. Spherical nucleic acids: Organized nucleotide aggregates as versatile nanomedicine. AGGREGATE (HOBOKEN, N.J.) 2022; 3:e120. [PMID: 35386748 PMCID: PMC8982904 DOI: 10.1002/agt2.120] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
Spherical nucleic acids (SNAs) are composed of a nanoparticle core and a layer of densely arranged oligonucleotide shells. After the first report of SNA by Mirkin and coworkers in 1996, it has created a significant interest by offering new possibilities in the field of gene and drug delivery. The controlled aggregation of oligonucleotides on the surface of organic/inorganic nanoparticles improves the delivery of genes and nucleic acid-based drugs and alters and regulates the biological profiles of the nanoparticle core within living organisms. Here in this review, we present an overview of the recent progress of SNAs that has speeded up their biomedical application and their potential transition to clinical use. We start with introducing the concept and characteristics of SNAs as drug/gene delivery systems and highlight recent efforts of bioengineering SNA by imaging and treatmenting various diseases. Finally, we discuss potential challenges and opportunities of SNAs, their ongoing clinical trials, and future translation, and how they may affect the current landscape of clinical practices. We hope that this review will update our current understanding of SNA, organized oligonucleotide aggregates, for disease diagnosis and treatment.
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Affiliation(s)
- Yangmeihui Song
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
| | - Wenyu Song
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
| | - Xiaoli Lan
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
| | - Weibo Cai
- Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Dawei Jiang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Molecular Imaging, Wuhan, China
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22
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Egloff S, Melnychuk N, Cruz Da Silva E, Reisch A, Martin S, Klymchenko AS. Amplified Fluorescence in Situ Hybridization by Small and Bright Dye-Loaded Polymeric Nanoparticles. ACS NANO 2022; 16:1381-1394. [PMID: 34928570 DOI: 10.1021/acsnano.1c09409] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Detection and imaging of RNA at the single-cell level is of utmost importance for fundamental research and clinical diagnostics. Current techniques of RNA analysis, including fluorescence in situ hybridization (FISH), are long, complex, and expensive. Here, we report a methodology of amplified FISH (AmpliFISH) that enables simpler and faster RNA imaging using small and ultrabright dye-loaded polymeric nanoparticles (NPs) functionalized with DNA. We found that the small size of NPs (below 20 nm) was essential for their access to the intracellular mRNA targets in fixed permeabilized cells. Moreover, proper selection of the polymer matrix of DNA-NPs minimized nonspecific intracellular interactions. Optimized DNA-NPs enabled sequence-specific imaging of different mRNA targets (survivin, actin, and polyA tails), using a simple 1 h staining protocol. Encapsulation of cyanine and rhodamine dyes with bulky counterions yielded green-, red-, and far-red-emitting NPs that were 2-100-fold brighter than corresponding quantum dots. These NPs enabled multiplexed detection of three mRNA targets simultaneously, showing distinctive mRNA expression profiles in three cancer cell lines. Image analysis confirmed the single-particle nature of the intracellular signal, suggesting single-molecule sensitivity of the method. AmpliFISH was found to be semiquantitative, correlating with RT-qPCR. In comparison with the commercial locked nucleic acid (LNA)-based FISH technique, AmpliFISH provides 8-200-fold stronger signal (dependent on the NP color) and requires only three steps vs ∼20 steps together with a much shorter time. Thus, combination of bright fluorescent polymeric NPs with FISH yields a fast and sensitive single-cell transcriptomic analysis method for RNA research and clinical diagnostics.
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Affiliation(s)
- Sylvie Egloff
- Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 74, Route du Rhin, 67401 Illkirch, France
| | - Nina Melnychuk
- Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 74, Route du Rhin, 67401 Illkirch, France
| | - Elisabete Cruz Da Silva
- Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 74, Route du Rhin, 67401 Illkirch, France
| | - Andreas Reisch
- Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 74, Route du Rhin, 67401 Illkirch, France
| | - Sophie Martin
- Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 74, Route du Rhin, 67401 Illkirch, France
| | - Andrey S Klymchenko
- Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 74, Route du Rhin, 67401 Illkirch, France
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23
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Diana A, Setzu MD, Kokaia Z, Nat R, Maxia C, Murtas D. SmartFlare TM is a reliable method for assessing mRNA expression in single neural stem cells. World J Stem Cells 2021; 13:1918-1927. [PMID: 35069990 PMCID: PMC8727230 DOI: 10.4252/wjsc.v13.i12.1918] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/11/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND One of the most challenging tasks of modern biology concerns the real-time tracking and quantification of mRNA expression in living cells. On this matter, a novel platform called SmartFlareTM has taken advantage of fluorophore-linked nanoconstructs for targeting RNA transcripts. Although fluorescence emission does not account for the spatial mRNA distribution, NanoFlare technology has grown a range of theranostic applications starting from detecting biomarkers related to diseases, such as cancer, neurodegenerative pathologies or embryonic developmental disorders.
AIM To investigate the potential of SmartFlareTM in determining time-dependent mRNA expression of prominin 1 (CD133) and octamer-binding transcription factor 4 (OCT4) in single living cells through differentiation.
METHODS Brain fragments from the striatum of aborted human fetuses aged 8 wk postconception were processed to obtain neurospheres. For the in vitro differentiation, neurospheres were gently dissociated with Accutase solution. Single cells were resuspended in a basic medium enriched with fetal bovine serum, plated on poly-L-lysine-coated glass coverslips, and grown in a lapse of time from 1 to 4 wk. Live cell mRNA detection was performed using SmartFlareTM probes (CD133, Oct4, Actin, and Scramble). All the samples were incubated at 37 °C for 24 h. For nuclear staining, Hoechst 33342 was added. SmartFlareTM CD133- and OCT4-specific fluorescence signal was assessed using a semiquantitative visual approach, taking into account the fluorescence intensity and the number of labeled cells.
RESULTS In agreement with previous PCR experiments, a unique expression trend was observed for CD133 and OCT4 genes until 7 d in vitro (DIV). Fluorescence resulted in a mixture of diffuse cytoplasmic and spotted-like pattern, also detectable in the contacting neural branches. From 15 to 30 DIV, only few cells showed a scattered fluorescent pattern, in line with the differentiation progression and coherent with mRNA downregulation of these stemness-related genes.
CONCLUSION SmartFlareTM appears to be a reliable, easy-to-handle tool for investigating CD133 and OCT4 expression in a neural stem cell model, preserving cell biological properties in anticipation of downstream experiments.
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Affiliation(s)
- Andrea Diana
- Department of Biomedical Sciences, University of Cagliari, Monserrato 09042, Cagliari, Italy
| | - Maria Dolores Setzu
- Department of Biomedical Sciences, University of Cagliari, Monserrato 09042, Cagliari, Italy
| | - Zaal Kokaia
- Laboratory of Stem Cells & Restorative Neurology, Lund Stem Cell Center, Lund University, Lund SE-221 84, Lund, Sweden
| | - Roxana Nat
- Institute of Neuroscience, Medical University of Innsbruck, Innsbruck 6020, Austria
| | - Cristina Maxia
- Department of Biomedical Sciences, University of Cagliari, Monserrato 09042, Cagliari, Italy
| | - Daniela Murtas
- Department of Biomedical Sciences, University of Cagliari, Monserrato 09042, Cagliari, Italy
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24
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Li J, Liu S, Wang J, Liu R, Yang X, Wang K, Huang J. Photocaged amplified FRET nanoflares: spatiotemporal controllable of mRNA-powered nanomachines for precise and sensitive microRNA imaging in live cells. Nucleic Acids Res 2021; 50:e40. [PMID: 34935962 PMCID: PMC9023253 DOI: 10.1093/nar/gkab1258] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 11/24/2021] [Accepted: 12/21/2021] [Indexed: 12/18/2022] Open
Abstract
There is considerable interest in creating a precise and sensitive strategy for in situ visualizing and profiling intracellular miRNA. Present here is a novel photocaged amplified FRET nanoflare (PAFN), which spatiotemporal controls of mRNA-powered nanomachine for precise and sensitive miRNA imaging in live cells. The PAFN could be activated remotely by light, be triggered by specific low-abundance miRNA and fueled by high-abundance mRNA. It offers high spatiotemporal control over the initial activity of nanomachine at desirable time and site, and a ‘one-to-more’ ratiometric signal amplification model. The PAFN, an unprecedented design, is quiescent during the delivery process. However, upon reaching the interest tumor site, it can be selectively activated by light, and then be triggered by specific miRNA, avoiding undesirable early activation and reducing nonspecific signals, allowing precise and sensitive detection of specific miRNA in live cells. This strategy may open new avenues for creating spatiotemporally controllable and endogenous molecule-powered nanomachine, facilitating application at biological and medical imaging.
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Affiliation(s)
- Jing Li
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, P.R. China.,School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, P.R. China
| | - Shiyuan Liu
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, P.R. China
| | - Jiaoli Wang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, P.R. China
| | - Ruiting Liu
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, P.R. China
| | - Xiaohai Yang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, P.R. China
| | - Kemin Wang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, P.R. China
| | - Jin Huang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, P.R. China
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25
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Bayoumi M, Munir M. Potential Use of CRISPR/Cas13 Machinery in Understanding Virus-Host Interaction. Front Microbiol 2021; 12:743580. [PMID: 34899631 PMCID: PMC8664230 DOI: 10.3389/fmicb.2021.743580] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 10/25/2021] [Indexed: 12/20/2022] Open
Abstract
Prokaryotes have evolutionarily acquired an immune system to fend off invading mobile genetic elements, including viral phages and plasmids. Through recognizing specific sequences of the invading nucleic acid, prokaryotes mediate a subsequent degradation process collectively referred to as the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) (CRISPR-Cas) system. The CRISPR-Cas systems are divided into two main classes depending on the structure of the effector Cas proteins. Class I systems have effector modules consisting of multiple proteins, while class II systems have a single multidomain effector. Additionally, the CRISPR-Cas systems can also be categorized into types depending on the spacer acquisition components and their evolutionary features, namely, types I-VI. Among CRISPR/Cas systems, Cas9 is one of the most common multidomain nucleases that identify, degrade, and modulate DNA. Importantly, variants of Cas proteins have recently been found to target RNA, especially the single-effector Cas13 nucleases. The Cas13 has revolutionized our ability to study and perturb RNAs in endogenous microenvironments. The Cas13 effectors offer an excellent candidate for developing novel research tools in virological and biotechnological fields. Herein, in this review, we aim to provide a comprehensive summary of the recent advances of Cas13s for targeting viral RNA for either RNA-mediated degradation or CRISPR-Cas13-based diagnostics. Additionally, we aim to provide an overview of the proposed applications that could revolutionize our understanding of viral-host interactions using Cas13-mediated approaches.
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Affiliation(s)
- Mahmoud Bayoumi
- Division of Biomedical and Life Sciences, Lancaster University, Lancaster, United Kingdom
- Virology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Muhammad Munir
- Division of Biomedical and Life Sciences, Lancaster University, Lancaster, United Kingdom
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26
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Savulescu AF, Brackin R, Bouilhol E, Dartigues B, Warrell JH, Pimentel MR, Beaume N, Fortunato IC, Dallongeville S, Boulle M, Soueidan H, Agou F, Schmoranzer J, Olivo-Marin JC, Franco CA, Gomes ER, Nikolski M, Mhlanga MM. Interrogating RNA and protein spatial subcellular distribution in smFISH data with DypFISH. CELL REPORTS METHODS 2021; 1:100068. [PMID: 35474672 PMCID: PMC9017151 DOI: 10.1016/j.crmeth.2021.100068] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 06/15/2021] [Accepted: 08/03/2021] [Indexed: 12/17/2022]
Abstract
Advances in single-cell RNA sequencing have allowed for the identification of cellular subtypes on the basis of quantification of the number of transcripts in each cell. However, cells might also differ in the spatial distribution of molecules, including RNAs. Here, we present DypFISH, an approach to quantitatively investigate the subcellular localization of RNA and protein. We introduce a range of analytical techniques to interrogate single-molecule RNA fluorescence in situ hybridization (smFISH) data in combination with protein immunolabeling. DypFISH is suited to study patterns of clustering of molecules, the association of mRNA-protein subcellular localization with microtubule organizing center orientation, and interdependence of mRNA-protein spatial distributions. We showcase how our analytical tools can achieve biological insights by utilizing cell micropatterning to constrain cellular architecture, which leads to reduction in subcellular mRNA distribution variation, allowing for the characterization of their localization patterns. Furthermore, we show that our method can be applied to physiological systems such as skeletal muscle fibers.
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Affiliation(s)
- Anca F. Savulescu
- Division of Chemical, Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, 7295 Cape Town, South Africa
| | - Robyn Brackin
- Advanced Medical Bioimaging, Charité – Universitätsmedizin, 10-117 Berlin, Germany
| | - Emmanuel Bouilhol
- Université de Bordeaux, Bordeaux Bioinformatics Center, 33000 Bordeaux, France
- Université de Bordeaux, CNRS, IBGC, UMR 5095, 33077 Bordeaux, France
| | - Benjamin Dartigues
- Université de Bordeaux, Bordeaux Bioinformatics Center, 33000 Bordeaux, France
| | - Jonathan H. Warrell
- Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520, USA
| | - Mafalda R. Pimentel
- Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal
| | - Nicolas Beaume
- Division of Chemical, Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, 7295 Cape Town, South Africa
| | - Isabela C. Fortunato
- Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal
| | | | - Mikaël Boulle
- Chemogenomic and Biological Screening Core Facility, C2RT, Department of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France
- Université de Paris, Sorbonne Paris Cité, Paris, France
| | - Hayssam Soueidan
- Université de Bordeaux, Bordeaux Bioinformatics Center, 33000 Bordeaux, France
| | - Fabrice Agou
- Chemogenomic and Biological Screening Core Facility, C2RT, Department of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France
- Department of Structural Biology and Chemistry, URA 2185, Pasteur Institute, Paris, France
| | - Jan Schmoranzer
- Advanced Medical Bioimaging, Charité – Universitätsmedizin, 10-117 Berlin, Germany
| | | | - Claudio A. Franco
- Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal
| | - Edgar R. Gomes
- Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, 1649-028 Lisbon, Portugal
| | - Macha Nikolski
- Université de Bordeaux, Bordeaux Bioinformatics Center, 33000 Bordeaux, France
- Université de Bordeaux, CNRS, IBGC, UMR 5095, 33077 Bordeaux, France
| | - Musa M. Mhlanga
- Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- Epigenomics & Single Cell Biophysics Group, Department of Cell Biology, FNWI, Radboud University, 6525 GA Nijmegen, the Netherlands
- Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
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27
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Zhou WJ, Li H, Zhang KK, Wang F, Chu X, Jiang JH. Genetically Encoded Sensor Enables Endogenous RNA Imaging with Conformation-Switching Induced Fluorogenic Proteins. J Am Chem Soc 2021; 143:14394-14401. [PMID: 34431301 DOI: 10.1021/jacs.1c07719] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Genetically encoded molecular tools are crucial for live cell RNA imaging, and few are available for endogenous RNA imaging. We develop a new genetically encoded sensor using conformation switching RNA induced fluorogenic proteins that enable multicolor and signal-amplified imaging of endogenous RNAs. The sensor system is designed with an RNA sensing module and a degron-fused fluorescent protein reporter. Target RNA induces conformation switching of the RNA sensing module to form RNA aptamers that stabilize the degron-fused protein for fluorogenic imaging. This sensor is demonstrated for high-contrast imaging of survivin mRNA abundance and dynamics in live cells. Moreover, the sensor system is extended to a multicolor palette by screening fluorogenic proteins of distinct colors, and engineered into a signal amplifier using the split fluorescent protein design. The sensor is further exploited for imaging lncRNA MALAT-1 and its translocation dynamics during mitosis. Our sensor system can afford a valuable platform for RNA imaging in biomedical research and clinical theranostics.
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Affiliation(s)
- Wen-Jing Zhou
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
| | - Hua Li
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
| | - Ke-Ke Zhang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
| | - Fenglin Wang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
| | - Xia Chu
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
| | - Jian-Hui Jiang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
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28
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Zhao J, Li Z, Shao Y, Hu W, Li L. Spatially Selective Imaging of Mitochondrial MicroRNAs via Optically Programmable Strand Displacement Reactions. Angew Chem Int Ed Engl 2021; 60:17937-17941. [PMID: 34117823 DOI: 10.1002/anie.202105696] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/25/2021] [Indexed: 12/14/2022]
Abstract
MicroRNA (miRNA) functions are tightly regulated by their sub-compartmental location in living cells, and the ability to imaging of mitochondrial miRNAs (mitomiRs) is essential for understanding of the related pathological processes. However, most existing DNA-based methods could not be used for this purpose. Here, we report the development of a DNA nanoreporter technology for imaging of mitomiRs in living cells through near-infrared (NIR) light-controlled DNA strand displacement reactions. The sensing function of the DNA nanoreporters are silent (OFF) during the delivery process, but can be photoactivated (ON) with NIR light after targeted mitochondrial localization, enabling spatially-restricted imaging of two types of cancer-related mitomiRs with improved detection accuracy. Furthermore, we demonstrate imaging of mitomiRs in vivo through spatiotemporally-controlled delivery and activation. Therefore, this study illustrates a simple methodology that may be broadly applicable for investigating the mitomiRs-associated physiological events.
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Affiliation(s)
- Jian Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.,College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100190, China
| | - Zhixiang Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.,Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin, 300072, China
| | - Yulei Shao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.,College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100190, China
| | - Wenping Hu
- Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin, 300072, China
| | - Lele Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.,College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100190, China
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29
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Spatially Selective Imaging of Mitochondrial MicroRNAs via Optically Programmable Strand Displacement Reactions. Angew Chem Int Ed Engl 2021. [DOI: 10.1002/ange.202105696] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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30
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Jiao K, Yan Q, Guo L, Qu Z, Cao S, Chen X, Li Q, Zhu Y, Li J, Wang L, Fan C, Wang F. Poly‐Adenine‐Based Spherical Nucleic Acids for Efficient Live‐Cell MicroRNA Capture. Angew Chem Int Ed Engl 2021. [DOI: 10.1002/ange.202017039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Kai Jiao
- Division of Physical Biology CAS Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China
- University of Chinese Academy of Sciences Beijing 100049 China
| | - Qinglong Yan
- Division of Physical Biology CAS Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China
- University of Chinese Academy of Sciences Beijing 100049 China
| | - Linjie Guo
- Division of Physical Biology CAS Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China
- University of Chinese Academy of Sciences Beijing 100049 China
| | - Zhibei Qu
- 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
| | - Shuting Cao
- Division of Physical Biology CAS Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China
- University of Chinese Academy of Sciences Beijing 100049 China
| | - Xiaoliang Chen
- 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
| | - Qian Li
- 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
| | - Ying Zhu
- Division of Physical Biology CAS Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China
- Bioimaging Center Shanghai Synchrotron Radiation Facility Zhangjiang Laboratory The Interdisciplinary Research Center Shanghai Advanced Research Institute Chinese Academy of Sciences Shanghai 201210 China
| | - Jiang Li
- Division of Physical Biology CAS Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Shanghai 201800 China
- 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
- Bioimaging Center Shanghai Synchrotron Radiation Facility Zhangjiang Laboratory The Interdisciplinary Research Center Shanghai Advanced Research Institute Chinese Academy of Sciences Shanghai 201210 China
| | - Lihua Wang
- Bioimaging Center Shanghai Synchrotron Radiation Facility Zhangjiang Laboratory The Interdisciplinary Research Center Shanghai Advanced Research Institute Chinese Academy of Sciences Shanghai 201210 China
| | - Chunhai Fan
- 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
- Institute of Molecular Medicine Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 China
| | - Fei Wang
- 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
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31
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Hong M, Sun H, Yang Q, Cheng S, Yu S, Fan S, Li C, Cui C, Tan W. A microRNA-21-responsive doxorubicin-releasing sticky-flare for synergistic anticancer with silencing of microRNA and chemotherapy. Sci China Chem 2021. [DOI: 10.1007/s11426-020-9973-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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32
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Labib M, Kelley SO. Circulating tumor cell profiling for precision oncology. Mol Oncol 2021; 15:1622-1646. [PMID: 33448107 PMCID: PMC8169448 DOI: 10.1002/1878-0261.12901] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/19/2020] [Accepted: 01/11/2021] [Indexed: 02/06/2023] Open
Abstract
Analysis of circulating tumor cells (CTCs) collected from patient's blood offers a broad range of opportunities in the field of precision oncology. With new advances in profiling technology, it is now possible to demonstrate an association between the molecular profiles of CTCs and tumor response to therapy. In this Review, we discuss mechanisms of tumor resistance to therapy and their link to phenotypic and genotypic properties of CTCs. We summarize key technologies used to isolate and analyze CTCs and discuss recent clinical studies that examined CTCs for genomic and proteomic predictors of responsiveness to therapy. We also point out current limitations that still hamper the implementation of CTCs into clinical practice. We finally reflect on how these shortcomings can be addressed with the likely contribution of multiparametric approaches and advanced data analytics.
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Affiliation(s)
- Mahmoud Labib
- Department of Pharmaceutical SciencesUniversity of TorontoCanada
| | - Shana O. Kelley
- Department of Pharmaceutical SciencesUniversity of TorontoCanada
- Institute for Biomaterials and Biomedical EngineeringUniversity of TorontoCanada
- Department of BiochemistryUniversity of TorontoCanada
- Department of ChemistryUniversity of TorontoCanada
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33
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Jiao K, Yan Q, Guo L, Qu Z, Cao S, Chen X, Li Q, Zhu Y, Li J, Wang L, Fan C, Wang F. Poly-Adenine-Based Spherical Nucleic Acids for Efficient Live-Cell MicroRNA Capture. Angew Chem Int Ed Engl 2021; 60:14438-14445. [PMID: 33851770 DOI: 10.1002/anie.202017039] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 03/27/2021] [Indexed: 11/11/2022]
Abstract
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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Affiliation(s)
- Kai Jiao
- Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Qinglong Yan
- Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Linjie Guo
- Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Zhibei Qu
- 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
| | - Shuting Cao
- Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xiaoliang Chen
- 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
| | - Qian Li
- 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
| | - Ying Zhu
- Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.,Bioimaging Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, The Interdisciplinary Research Center, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Jiang Li
- Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800, China.,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.,Bioimaging Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, The Interdisciplinary Research Center, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Lihua Wang
- Bioimaging Center, Shanghai Synchrotron Radiation Facility, Zhangjiang Laboratory, The Interdisciplinary Research Center, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Chunhai Fan
- 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.,Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
| | - Fei Wang
- 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
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34
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Xue C, Hu S, Gao ZH, Wang L, Luo MX, Yu X, Li BF, Shen Z, Wu ZS. Programmably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs. Nat Commun 2021; 12:2928. [PMID: 34006888 PMCID: PMC8131747 DOI: 10.1038/s41467-021-23250-5] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 04/13/2021] [Indexed: 02/06/2023] Open
Abstract
Small interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.
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Affiliation(s)
- Chang Xue
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China
| | - Shuyao Hu
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China
| | - Zhi-Hua Gao
- Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medicine Genetics, School of Laboratory Medicine and Life Sciences, Institute of Functional Nucleic Acids and Personalized Cancer Theranostics, Wenzhou Medical University, Wenzhou, 325035, China
| | - Lei Wang
- Hunan Provincial Key Laboratory of Phytohormones and Growth Development, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, 410128, China
| | - Meng-Xue Luo
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China
| | - Xin Yu
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China
| | - Bi-Fei Li
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China
| | - Zhifa Shen
- Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medicine Genetics, School of Laboratory Medicine and Life Sciences, Institute of Functional Nucleic Acids and Personalized Cancer Theranostics, Wenzhou Medical University, Wenzhou, 325035, China
| | - Zai-Sheng Wu
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
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35
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Fukumoto S, Kawade M, Kimura K, Akiyama Y, Kikuchi A. Preparation of Spherical Nucleic Acid Nanoparticles Containing a Self-immolative Poly(carbamate) Core. ANAL SCI 2021; 37:781-784. [PMID: 33487596 DOI: 10.2116/analsci.20scn06] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
We prepared a novel spherical nucleic acid, containing a core structure of self-immolative poly(carbamate) (PC), with aminobenzyl alcohol as a repeating unit, by conjugating an end-activated PC derivative with an amine-terminated oligoDNA on a solid support for PC-oligoDNA. Dynamic light-scattering measurements revealed a hydrodynamic diameter of 107 nm with a narrow size distribution. A fluorescent monomer with aminobenzyl alcohol is available for PC-oligoDNA synthesis to enhance the fluorescence emission by a domino-like disassembly of PC in response to various external stimuli.
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Affiliation(s)
- Shione Fukumoto
- Department of Materials Science and Technology, Tokyo University of Science
| | - Mami Kawade
- Department of Materials Science and Technology, Tokyo University of Science
| | - Kazunori Kimura
- Department of Materials Science and Technology, Tokyo University of Science
| | - Yoshitsugu Akiyama
- Faculty of Industrial Science and Technology, Tokyo University of Science
| | - Akihiko Kikuchi
- Department of Materials Science and Technology, Tokyo University of Science
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36
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Shao Y, Zhao J, Yuan J, Zhao Y, Li L. Organelle‐Specific Photoactivation of DNA Nanosensors for Precise Profiling of Subcellular Enzymatic Activity. Angew Chem Int Ed Engl 2021. [DOI: 10.1002/ange.202016738] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- Yulei Shao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
- College of Materials Science and Optoelectronic Technology University of Chinese Academy of Sciences Beijing 100149 China
- Department of Chemistry Tsinghua University Beijing 100084 China
| | - Jian Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
- College of Materials Science and Optoelectronic Technology University of Chinese Academy of Sciences Beijing 100149 China
| | - Jinying Yuan
- Department of Chemistry Tsinghua University Beijing 100084 China
| | - Yuliang Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
| | - Lele Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
- College of Materials Science and Optoelectronic Technology University of Chinese Academy of Sciences Beijing 100149 China
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Shao Y, Zhao J, Yuan J, Zhao Y, Li L. Organelle‐Specific Photoactivation of DNA Nanosensors for Precise Profiling of Subcellular Enzymatic Activity. Angew Chem Int Ed Engl 2021; 60:8923-8931. [DOI: 10.1002/anie.202016738] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Indexed: 12/12/2022]
Affiliation(s)
- Yulei Shao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
- College of Materials Science and Optoelectronic Technology University of Chinese Academy of Sciences Beijing 100149 China
- Department of Chemistry Tsinghua University Beijing 100084 China
| | - Jian Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
- College of Materials Science and Optoelectronic Technology University of Chinese Academy of Sciences Beijing 100149 China
| | - Jinying Yuan
- Department of Chemistry Tsinghua University Beijing 100084 China
| | - Yuliang Zhao
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
| | - Lele Li
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
- College of Materials Science and Optoelectronic Technology University of Chinese Academy of Sciences Beijing 100149 China
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38
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A Miniaturized Platform for Multiplexed Drug Response Imaging in Live Tumors. Cancers (Basel) 2021; 13:cancers13040653. [PMID: 33562152 PMCID: PMC7915324 DOI: 10.3390/cancers13040653] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 01/29/2021] [Accepted: 02/01/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary We have developed an implantable microdevice that is placed into a live tumor, and can directly image how effective various chemotherapy drugs are at inducing cell death, without having to remove or process the tumor tissue. Currently drug optimization is performed by assessing tumor shrinkage after treating a patient with systemic doses of a chemotherapy agent; this only evaluates a single treatment at a time and typically takes weeks-months before an optimal treatment strategy is found (if found at all) for a specific patient. In contrast, using the technology presented here, a personalized cancer treatment strategy can potentially be optimized and tailored to a specific patient’s tumor characteristics within several hours, without requiring surgical tissue removal or prolonged trials of potentially ineffective chemotherapies. Abstract By observing the activity of anti-cancer agents directly in tumors, there is potential to greatly expand our understanding of drug response and develop more personalized cancer treatments. Implantable microdevices (IMD) have been recently developed to deliver microdoses of chemotherapeutic agents locally into confined regions of live tumors; the tissue can be subsequently removed and analyzed to evaluate drug response. This method has the potential to rapidly screen multiple drugs, but requires surgical tissue removal and only evaluates drug response at a single timepoint when the tissue is excised. Here, we describe a “lab-in-a-tumor” implantable microdevice (LIT-IMD) platform to image cell-death drug response within a live tumor, without requiring surgical resection or tissue processing. The LIT-IMD is inserted into a live tumor and delivers multiple drug microdoses into spatially discrete locations. In parallel, it locally delivers microdose levels of a fluorescent cell-death assay, which diffuses into drug-exposed tissues and accumulates at sites of cell death. An integrated miniaturized fluorescence imaging probe images each region to evaluate drug-induced cell death. We demonstrate ability to evaluate multi-drug response over 8 h using murine tumor models and show correlation with gold-standard conventional fluorescence microscopy and histopathology. This is the first demonstration of a fully integrated platform for evaluating multiple chemotherapy responses in situ. This approach could enable a more complete understanding of drug activity in live tumors, and could expand the utility of drug-response measurements to a wide range of settings where surgery is not feasible.
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Zhang S, Shen J, Li D, Cheng Y. Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing. Theranostics 2021; 11:614-648. [PMID: 33391496 PMCID: PMC7738854 DOI: 10.7150/thno.47007] [Citation(s) in RCA: 227] [Impact Index Per Article: 56.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 08/31/2020] [Indexed: 12/26/2022] Open
Abstract
CRISPR/Cas9 genome editing has gained rapidly increasing attentions in recent years, however, the translation of this biotechnology into therapy has been hindered by efficient delivery of CRISPR/Cas9 materials into target cells. Direct delivery of CRISPR/Cas9 system as a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA (sgRNA) has emerged as a powerful and widespread method for genome editing due to its advantages of transient genome editing and reduced off-target effects. In this review, we summarized the current Cas9 RNP delivery systems including physical approaches and synthetic carriers. The mechanisms and beneficial roles of these strategies in intracellular Cas9 RNP delivery were reviewed. Examples in the development of stimuli-responsive and targeted carriers for RNP delivery are highlighted. Finally, the challenges of current Cas9 RNP delivery systems and perspectives in rational design of next generation materials for this promising field will be discussed.
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Affiliation(s)
- Song Zhang
- South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou 510640, China
| | - Jiangtao Shen
- The Second People's Hospital of Taizhou affiliated to Yangzhou University, Taizhou, 225500, China
| | - Dali Li
- Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai 200241, China
| | - Yiyun Cheng
- South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou 510640, China
- Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai 200241, China
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40
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Holmes TR, Paller AS. Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders. Pharmaceuticals (Basel) 2020; 13:E360. [PMID: 33147737 PMCID: PMC7693734 DOI: 10.3390/ph13110360] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 10/28/2020] [Accepted: 10/30/2020] [Indexed: 11/23/2022] Open
Abstract
Spherical nucleic acids (SNAs) are nanostructures consisting of nucleic acids in a spherical configuration, often around a nanoparticle core. SNAs are advantageous as gene-regulating agents compared to conventional gene therapy owing to their low toxicity, enhanced stability, uptake by virtually any cell, and ability to penetrate the epidermal barrier. In this review we: (i) describe the production, structure and properties of SNAs; (ii) detail the mechanism of SNA uptake in keratinocytes, regulated by scavenger receptors; and (iii) report how SNAs have been topically applied and intralesionally injected for skin disorders. Specialized SNAs called nanoflares can be topically applied for gene-based diagnosis (scar vs. normal tissue). Topical SNAs directed against TNFα and interleukin-17A receptor reversed psoriasis-like disease in mouse models and have been tested in Phase 1 human trials. Furthermore, SNAs targeting ganglioside GM3 synthase accelerate wound healing in diabetic mouse models. Most recently, SNAs targeting toll-like receptor 9 are being used in Phase 2 human trials via intratumoral injection to induce immune responses in Merkel cell and cutaneous squamous cell carcinoma. Overall, SNAs are a valuable tool in bench-top and clinical research, and their advantageous properties, including penetration into the epidermis after topical delivery, provide new opportunities for targeted therapies.
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Affiliation(s)
| | - Amy S. Paller
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA;
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Yeldell SB, Yang L, Lee J, Eberwine JH, Dmochowski IJ. Oligonucleotide Probe for Transcriptome in Vivo Analysis (TIVA) of Single Neurons with Minimal Background. ACS Chem Biol 2020; 15:2714-2721. [PMID: 32902259 DOI: 10.1021/acschembio.0c00499] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Messenger RNA (mRNA) isolated from single cells can generate powerful biological insights, including the discovery of new cell types with unique functions as well as markers potentially predicting a cell's response to various therapeutic agents. We previously introduced an oligonucleotide-based technique for site-selective, photoinduced biotinylation and capture of mRNA within a living cell called transcriptome in vivo analysis (TIVA). Successful application of the TIVA technique hinges upon its oligonucleotide probe remaining completely inert (or "caged") to mRNA unless photoactivated. To improve the reliability of TIVA probe caging in diverse and challenging biological conditions, we applied a rational design process involving iterative modifications to the oligonucleotide construct. In this work, we discuss these design motivations and present an optimized probe with minimal background binding to mRNA prior to photolysis. We assess its caging performance through multiple in vitro assays including FRET analysis, native gel comigration, and pull down with model mRNA transcripts. Finally, we demonstrate that this improved probe can also isolate mRNA from single living neurons in brain tissue slices with excellent caging control.
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Affiliation(s)
- Sean B. Yeldell
- Department of Chemistry, University of Pennsylvania, 231 South 34 Street, Philadelphia, Pennsylvania 19104-6323, United States
| | - Linlin Yang
- Department of Chemistry, University of Pennsylvania, 231 South 34 Street, Philadelphia, Pennsylvania 19104-6323, United States
| | - Jaehee Lee
- Department of Pharmacology, University of Pennsylvania, 38 John Morgan Building, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104-6084, United States
| | - James H. Eberwine
- Department of Pharmacology, University of Pennsylvania, 38 John Morgan Building, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104-6084, United States
| | - Ivan J. Dmochowski
- Department of Chemistry, University of Pennsylvania, 231 South 34 Street, Philadelphia, Pennsylvania 19104-6323, United States
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42
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Liu R, Zhang S, Zheng TT, Chen YR, Wu JT, Wu ZS. Intracellular Nonenzymatic In Situ Growth of Three-Dimensional DNA Nanostructures for Imaging Specific Biomolecules in Living Cells. ACS NANO 2020; 14:9572-9584. [PMID: 32806042 DOI: 10.1021/acsnano.9b09995] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Real-time in situ monitoring of low-abundance cancer biomarkers (e.g., miRNAs and proteins) in living cells by nonenzymatic assembly entirely from original DNA probes remains unexplored due to an extremely complex intracellular environment. Herein, a nonenzymatic palindrome-catalyzed DNA assembly (NEPA) technique is developed to execute the in situ imaging of intracellular miRNAs by assembling a three-dimensional nanoscale DNA spherical structure (NS) with low mobility from three free hairpin-type DNAs rather than from DNA intermediates based on the interaction of designed terminal palindromes. Target miRNA was detected down to 1.4 pM, and its family members were distinguished with almost 100% accuracy. The subcellular localization of NS products can be visualized in real time. The NEPA-based sensing strategy is also suitable for the intracellular in situ fluorescence imaging of cancer-related protein receptors, offering valuable insight into developing sensing protocols for understanding the biological function of vital biomolecules in disease pathogenesis and future therapeutic applications.
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Affiliation(s)
- Ran Liu
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China
| | - Songbai Zhang
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China
- College of Chemistry and Materials Engineering, Hunan University of Arts and Science, Changde 415000, China
| | - Ting-Ting Zheng
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China
| | - Yan-Ru Chen
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China
| | - Jing-Ting Wu
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China
| | - Zai-Sheng Wu
- Cancer Metastasis Alert and Prevention Center, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, National and Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China
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43
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Labib M, Philpott DN, Wang Z, Nemr C, Chen JB, Sargent EH, Kelley SO. Magnetic Ranking Cytometry: Profiling Rare Cells at the Single-Cell Level. Acc Chem Res 2020; 53:1445-1457. [PMID: 32662263 DOI: 10.1021/acs.accounts.0c00179] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Cellular heterogeneity in biological systems presents major challenges in the diagnosis and treatment of disease and also complicates the deconvolution of complex cellular phenomena. Single-cell analysis methods provide information that is not masked by the intrinsic heterogeneity of the bulk population and can therefore be applied to gain insights into heterogeneity among different cell subpopulations with fine resolution. Over the last 5 years, an explosion in the number of single-cell measurement methods has occurred. However, most of these methods are applicable to pure populations of cultured cells and are not able to handle high levels of phenotypic heterogeneity or a large background of nontarget cells. Microfluidics is an attractive tool for single cell manipulation as it enables individual encasing of single cells, allowing for high-throughput analysis with precise control of the local environment. Our laboratory has developed a new microfluidics-based analytical strategy to meet this unmet need referred to as magnetic ranking cytometry (MagRC). Cells expressing a biomarker of interest are labeled with receptor-coated magnetic nanoparticles and isolated from nontarget cells using a microfluidic device. The device ranks the cells according to the level of bound magnetic nanoparticles, which corresponds to the expression level of a target biomarker. Over the last several years, two generations of MagRC devices have been developed for different applications. The first-generation MagRC devices are powerful tools for the quantitation and analysis of rare cells present in heterogeneous samples, such as circulating tumor cells, stem cells, and pathogenic bacteria. The second-generation MagRC devices are compatible with the efficient recovery of cells sorted on the basis of protein expression and can be used to analyze large populations of cells and perform phenotypic CRISPR screens. To improve analytical precision, newer iterations of the first-generation and second-generation MagRC devices have been integrated with electrochemical sensors and Hall effect sensors, respectively. Both generations of MagRC devices permit the isolation of viable cells, which sets the stage for a wide range of applications, such as generating cell lines from rare cells and in vitro screening for effective therapeutic interventions in cancer patients to realize the promise of personalized medicine. This Account summarizes the development and application of the MagRC and describes a suite of advances that have enabled single-cell tumor cell analysis and monitoring tumor response to therapy, stem cell analysis, and detection of pathogens.
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Affiliation(s)
- Mahmoud Labib
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2, Canada
| | - David N. Philpott
- Department of Electrical & Computer Engineering, University of Toronto, Toronto, Ontario M5S 1A8, Canada
| | - Zongjie Wang
- Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada
| | - Carine Nemr
- Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3G4, Canada
| | - Jenise B. Chen
- Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3G4, Canada
| | - Edward H. Sargent
- Department of Electrical & Computer Engineering, University of Toronto, Toronto, Ontario M5S 1A8, Canada
| | - Shana O. Kelley
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2, Canada
- Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada
- Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
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44
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Ribbon of DNA Lattice on Gold Nanoparticles for Selective Drug Delivery to Cancer Cells. Angew Chem Int Ed Engl 2020. [DOI: 10.1002/ange.202005624] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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45
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Zhang S, Chen C, Xue C, Chang D, Xu H, Salena BJ, Li Y, Wu Z. Ribbon of DNA Lattice on Gold Nanoparticles for Selective Drug Delivery to Cancer Cells. Angew Chem Int Ed Engl 2020; 59:14584-14592. [DOI: 10.1002/anie.202005624] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/21/2020] [Indexed: 12/25/2022]
Affiliation(s)
- Shuxin Zhang
- Cancer Metastasis Alert and Prevention Center Fujian Provincial Key Laboratory of Cancer Metastasis, Chemoprevention and Chemotherapy National & Local Joint Biomedical Engineering Research Center on, Photodynamic Technologies Pharmaceutical Photocatalysis of State Key Laboratory of, Photocatalysis on Energy and Environment College of Chemistry Fuzhou University Fuzhou 350002 China
| | - Chang Chen
- Cancer Metastasis Alert and Prevention Center Fujian Provincial Key Laboratory of Cancer Metastasis, Chemoprevention and Chemotherapy National & Local Joint Biomedical Engineering Research Center on, Photodynamic Technologies Pharmaceutical Photocatalysis of State Key Laboratory of, Photocatalysis on Energy and Environment College of Chemistry Fuzhou University Fuzhou 350002 China
| | - Chang Xue
- Cancer Metastasis Alert and Prevention Center Fujian Provincial Key Laboratory of Cancer Metastasis, Chemoprevention and Chemotherapy National & Local Joint Biomedical Engineering Research Center on, Photodynamic Technologies Pharmaceutical Photocatalysis of State Key Laboratory of, Photocatalysis on Energy and Environment College of Chemistry Fuzhou University Fuzhou 350002 China
| | - Dingran Chang
- Department of Biochemistry and Biomedical Sciences McMaster University 1280 Main Street West Hamilton Ontario L8S4K1 Canada
| | - Huo Xu
- Cancer Metastasis Alert and Prevention Center Fujian Provincial Key Laboratory of Cancer Metastasis, Chemoprevention and Chemotherapy National & Local Joint Biomedical Engineering Research Center on, Photodynamic Technologies Pharmaceutical Photocatalysis of State Key Laboratory of, Photocatalysis on Energy and Environment College of Chemistry Fuzhou University Fuzhou 350002 China
| | - Bruno J. Salena
- Department of Medicine McMaster University 1280 Main Street West Hamilton Ontario L8S4K1 Canada
| | - Yingfu Li
- Department of Biochemistry and Biomedical Sciences McMaster University 1280 Main Street West Hamilton Ontario L8S4K1 Canada
| | - Zai‐Sheng Wu
- Cancer Metastasis Alert and Prevention Center Fujian Provincial Key Laboratory of Cancer Metastasis, Chemoprevention and Chemotherapy National & Local Joint Biomedical Engineering Research Center on, Photodynamic Technologies Pharmaceutical Photocatalysis of State Key Laboratory of, Photocatalysis on Energy and Environment College of Chemistry Fuzhou University Fuzhou 350002 China
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Golab K, Krzystyniak A, Langa P, Pikuła M, Kunovac S, Borek P, Trzonkowski P, Millis JM, Fung J, Witkowski P. Effect of serum on SmartFlare™ RNA Probes uptake and detection in cultured human cells. BIOMEDICAL JOURNAL OF SCIENTIFIC & TECHNICAL RESEARCH 2020; 28:21788-21793. [PMID: 32851205 PMCID: PMC7447198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
SmartFlare™ RNA Detection Probes from Millipore is a novel technology to detect RNA in live cells based on the use of 12 nm gold nanoparticles coated with nucleotides. We proved that SmartFlares™ are internalized by human primary lymphocytes. However, fluorescence signals from target RNA detection can only be observed in the presence of Fetal Bovine Serum (FBS) in the medium, whereas it is not detectable without FBS or when medium is supplemented with human albumin. Image analysis of fluorescence generated from SmartFlare™ Uptake Control (gives constant signal regardless of contact with RNA) and RNA Specific Probes revealed further differences. In the presence of FBS, the fluorescence signal for both reagents was diffused within the cells, whereas in the absence of FBS, it was detected as single spots within the cells only when the Uptake Control was used. It is possible that FBS components are necessary for SmartFlare™ Probes to be released from cellular compartments into the cytoplasm where they can get into contact with target RNA. The exact mechanism of this phenomena should be further determined. However, for the first time, we present here that FBS in the cell culture medium is essential for RNA detection by SmartFlare™ technology in human lymphocytes.
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Affiliation(s)
- Karolina Golab
- Department of Surgery, University of Chicago, Chicago, IL, USA
| | - Adam Krzystyniak
- Department of Surgery, University of Chicago, Chicago, IL, USA
- Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk, Poland
- Laboratory of Cell Biophysics, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Warsaw, Poland
| | - Paulina Langa
- Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk, Poland
- Microsurgery Research, Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, USA
| | - Michał Pikuła
- Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk, Poland
- Laboratory of Tissue Engineering and Regenerative Medicine, Department of Embryology, Medical University of Gdansk, Gdansk, Poland
| | - Stefan Kunovac
- Department of Surgery, University of Chicago, Chicago, IL, USA
| | - Peter Borek
- Department of Surgery, University of Chicago, Chicago, IL, USA
| | - Piotr Trzonkowski
- Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk, Poland
| | | | - John Fung
- Department of Surgery, University of Chicago, Chicago, IL, USA
| | - Piotr Witkowski
- Department of Surgery, University of Chicago, Chicago, IL, USA
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Ebrahimi SB, Samanta D, Mirkin CA. DNA-Based Nanostructures for Live-Cell Analysis. J Am Chem Soc 2020; 142:11343-11356. [DOI: 10.1021/jacs.0c04978] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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48
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Photoactivatable fluorescent probes for spatiotemporal-controlled biosensing and imaging. Trends Analyt Chem 2020. [DOI: 10.1016/j.trac.2020.115811] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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49
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Samanta D, Ebrahimi SB, Mirkin CA. Nucleic-Acid Structures as Intracellular Probes for Live Cells. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2020; 32:e1901743. [PMID: 31271253 PMCID: PMC6942251 DOI: 10.1002/adma.201901743] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 05/08/2019] [Indexed: 05/02/2023]
Abstract
The chemical composition of cells at the molecular level determines their growth, differentiation, structure, and function. Probing this composition is powerful because it provides invaluable insight into chemical processes inside cells and in certain cases allows disease diagnosis based on molecular profiles. However, many techniques analyze fixed cells or lysates of bulk populations, in which information about dynamics and cellular heterogeneity is lost. Recently, nucleic-acid-based probes have emerged as a promising platform for the detection of a wide variety of intracellular analytes in live cells with single-cell resolution. Recent advances in this field are described and common strategies for probe design, types of targets that can be identified, current limitations, and future directions are discussed.
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Affiliation(s)
- Devleena Samanta
- Department of Chemistry and International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA
| | - Sasha B Ebrahimi
- Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA
| | - Chad A Mirkin
- Department of Chemistry and International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA
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50
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Zhang Y, Li M, Gao X, Chen Y, Liu T. Nanotechnology in cancer diagnosis: progress, challenges and opportunities. J Hematol Oncol 2019; 12:137. [PMID: 31847897 PMCID: PMC6918551 DOI: 10.1186/s13045-019-0833-3] [Citation(s) in RCA: 250] [Impact Index Per Article: 41.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 11/18/2019] [Indexed: 12/24/2022] Open
Abstract
In the fight against cancer, early detection is a key factor for successful treatment. However, the detection of cancer in the early stage has been hindered by the intrinsic limits of conventional cancer diagnostic methods. Nanotechnology provides high sensitivity, specificity, and multiplexed measurement capacity and has therefore been investigated for the detection of extracellular cancer biomarkers and cancer cells, as well as for in vivo imaging. This review summarizes the latest developments in nanotechnology applications for cancer diagnosis. In addition, the challenges in the translation of nanotechnology-based diagnostic methods into clinical applications are discussed.
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Affiliation(s)
- Ye Zhang
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, 410008, China
| | - Maoyu Li
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, 410008, China
- Department of Gastroenterology, XiangYa Hospital, Central South University, Changsha, 410008, China
| | - Xiaomei Gao
- Department of Pathology, XiangYa Hospital, Central South University, Changsha, 410008, China
| | - Yongheng Chen
- Department of Oncology, NHC Key Laboratory of Cancer Proteomics, XiangYa Hospital, Central South University, Changsha, 410008, China.
| | - Ting Liu
- Department of Gastroenterology, XiangYa Hospital, Central South University, Changsha, 410008, China.
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