24 results on '"Si Si Liew"'
Search Results
2. Cell-Permeant Bioadaptors for Cytosolic Delivery of Native Antibodies: A 'Mix-and-Go' Approach
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Shubo Du, Si Si Liew, Cheng-wu Zhang, Wei Du, Wenjie Lang, Cassandra C. Y. Yao, Lin Li, Jingyan Ge, and Shao Q. Yao
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Chemistry ,QD1-999 - Published
- 2020
- Full Text
- View/download PDF
3. Cell-penetrating poly(disulfide)-based nanoquenchers (qCPDs) for self-monitoring of intracellular gene delivery
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Wenjie Lang, Si Si Liew, Shuyi Wang, Dawei Hong, Liquan Zhu, Shubo Du, Linye Jiang, Shao Q. Yao, and Jingyan Ge
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Materials Chemistry ,Metals and Alloys ,Ceramics and Composites ,General Chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials - Abstract
Cell-penetrating poly(disulfide)-based nanoquenchers (qCPDs) were developed for both gene delivery and detection of gene release.
- Published
- 2022
4. Renal-Clearable Molecular Probe for Near-Infrared Fluorescence Imaging and Urinalysis of SARS-CoV-2
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Ziling Zeng, Chi Zhang, Si Si Liew, Kanyi Pu, Shasha He, Penghui Cheng, School of Chemical and Biomedical Engineering, School of Physical and Mathematical Sciences, and Lee Kong Chian School of Medicine (LKCMedicine)
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Bioengineering [Engineering] ,Near-Infrared Fluorescence Imaging ,Fluorophore ,medicine.medical_treatment ,Urinalysis ,Kidney ,Biochemistry ,Catalysis ,Viral Matrix Proteins ,Mice ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,In vivo ,Fluorescence Imaging ,medicine ,Animals ,Humans ,skin and connective tissue diseases ,Lung ,Fluorescent Dyes ,Spectroscopy, Near-Infrared ,Protease ,Viral matrix protein ,SARS-CoV-2 ,Chemistry ,Communication ,Optical Imaging ,fungi ,Chemical engineering [Engineering] ,COVID-19 ,Kidney metabolism ,General Chemistry ,body regions ,Viral replication ,Molecular Probes ,Biophysics ,Molecular probe - Abstract
Despite the importance of rapid and accurate detection of SARS-CoV-2 in controlling the COVID-19 pandemic, current diagnostic methods are static and unable to distinguish between viable/nonviable virus or directly reflect viral replication activity. Real-time imaging of protease activity specific to SARS-CoV-2 can overcome these issues but remains lacking. Herein, we report a near-infrared fluorescence (NIRF) activatable molecular probe (SARS-CyCD) for detection of SARS-CoV-2 protease in living mice. The probe comprises a hemicyanine fluorophore caged with a protease peptide substrate and a cyclodextrin unit, which function as an NIRF signaling moiety and a renal-clearable enabler, respectively. The peptide substrate of SARS-CyCD can be specifically cleaved by SARS-CoV-2 main protease (Mpro), resulting in NIRF signal activation and liberation of the renal-clearable fluorescent fragment (CyCD). Such a design not only allows sensitive detection of Mpro in the lungs of living mice after intratracheal administration but also permits optical urinalysis of SARS-CoV-2 infection. Thus, this study presents an in vivo sensor that holds potential in preclinical high-throughput drug screening and clinical diagnostics for respiratory viral infections. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) K.P. thanks Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20), Academic Research Fund Tier 2 (MOE2018-T2-2-042), and A*STAR SERC AME Programmatic Fund (SERC A18A8b0059) for the financial support.
- Published
- 2021
5. Hemicyanine‐Based Near‐Infrared Activatable Probes for Imaging and Diagnosis of Diseases
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Si Si Liew, Xin Wei, Ziling Zeng, Kanyi Pu, School of Chemical and Biomedical Engineering, and School of Physical and Mathematical Sciences
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Bioengineering [Engineering] ,Inflammation ,Fluorescence-lifetime imaging microscopy ,Infrared Rays ,Chemistry ,Optical Imaging ,Near-infrared spectroscopy ,Design elements and principles ,Structural diversity ,General Medicine ,General Chemistry ,Computational biology ,Carbocyanines ,Activatable Probes ,Skin Diseases ,Catalysis ,Intestinal Diseases ,Preclinical research ,Optical imaging ,Neoplasms ,Clinical diagnosis ,Chemistry [Science] ,Humans ,Preclinical imaging ,Fluorescent Dyes - Abstract
Molecular activatable probes with near-infrared (NIR) fluorescence play a critical role in in vivo imaging of biomarkers for drug screening and disease diagnosis. With structural diversity and high fluorescence quantum yields, hemicyanine dyes have emerged as a versatile scaffold for the construction of activatable optical probes. This Review presents a survey of hemicyanine-based NIR activatable probes (HNAPs) for in vivo imaging and early diagnosis of diseases. The molecular design principles of HNAPs towards activatable optical signaling against various biomarkers are discussed with a focus on their broad applications in the detection of diseases including inflammation, acute organ failure, skin diseases, intestinal diseases, and cancer. This progress not only proves the unique value of HNAPs in preclinical research but also highlights their high translational potential in clinical diagnosis. Ministry of Education (MOE) K.P. thanks Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20), Academic Research Fund Tier 2 (MOE2018-T2-2-042), and A*STAR SERC AME Programmatic Fund (SERCA18A8b0059) for the financial support.
- Published
- 2021
6. Chemiluminescent Probes with Long‐Lasting High Brightness for In Vivo Imaging of Neutrophils
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Jingsheng Huang, Penghui Cheng, Cheng Xu, Si Si Liew, Shasha He, Yan Zhang, Kanyi Pu, School of Chemical and Biomedical Engineering, Lee Kong Chian School of Medicine (LKCMedicine), and School of Physical and Mathematical Sciences
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Bioengineering [Engineering] ,Mice ,Luminescence ,Neutrophils ,Chemiluminescence Probe ,Luminescent Measurements ,Optical Imaging ,Animals ,Medicine [Science] ,General Chemistry ,General Medicine ,Bioimaging ,Catalysis - Abstract
Real-time optical imaging of immune cells can contribute to understanding their pathophysiological roles, which still remains challenging. Current sensitive chemiluminophores have issues of short half-lives and low brightness, limiting their ability for in vivo longitudinal monitoring of immunological processes. To tackle these issues, we report benzoazole-phenoxyl-dioxetane (BAPD)-based chemiluminophores with intramolecular hydrogen bonding for in vivo imaging of neutrophils. Compared with the classical counterpart, chemiluminescence half-lives and brightness of BAPDs in the aqueous solution are increased by ∼ 33- and 8.2-fold, respectively. Based on the BAPD scaffold, a neutrophil elastase-responsive chemiluminescent probe is developed for real-time imaging of neutrophils in peritonitis and psoriasis mouse models. Our study provides an intramolecular hydrogen bonding molecular design for improving the performance of chemiluminophores in advanced imaging applications. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) K.P. thanks Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19; RT05/20), Academic Research Fund Tier 2 (MOE2018-T2-2-042; MOE-T2EP30220-0010), and A*STAR SERC AME Programmatic Fund (SERC A18A8b0059) for the financial support.
- Published
- 2022
7. Cell-Permeant Bioadaptors for Cytosolic Delivery of Native Antibodies: A 'Mix-and-Go' Approach
- Author
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Wenjie Lang, Cheng-Wu Zhang, Si Si Liew, Lin Li, Wei Du, Jingyan Ge, Shao Q. Yao, Cassandra C Y Yao, and Shubo Du
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biology ,010405 organic chemistry ,Chemistry ,Drug discovery ,General Chemical Engineering ,Cell ,Chemical biology ,General Chemistry ,Protein degradation ,010402 general chemistry ,Protein glutathionylation ,01 natural sciences ,0104 chemical sciences ,Cell biology ,Cell membrane ,medicine.anatomical_structure ,medicine ,biology.protein ,Protein A ,QD1-999 ,Intracellular ,Research Article - Abstract
Antibodies are powerful tools that may potentially find wide applications in live-cell bioimaging, disease diagnostics, and therapeutics. Their practical applications have however remained limited thus far, owing to their inability to cross the cell membrane. Existing approaches for cytosolic delivery of functional antibodies are available, but they are constantly plagued by the need for chemical/genetic modifications, low delivery efficiency, and severe endolysosomal trapping. Consequently, it is of paramount importance to develop new strategies capable of highly efficient cytosolic delivery of native antibodies with immediate bioavailability. Herein, we report a modification-free, convenient “mix-and-go” strategy for the cytosolic delivery of native antibodies to different live mammalian cells efficiently, with minimal endolysosomal trapping and immediate bioavailability. By simply mixing a cell-permeant bioadaptor (derived from protein A or TRIM21) with a commercially available off-the-shelf antibody, the resulting noncovalent complex could be immediately used for intracellular delivery of native antibodies needed in subsequent cytosolic target engagement. The versatility of this approach was successfully illustrated in a number of applications, including antibody-based, live-cell imaging of the endogenous protein glutathionylation to detect oxidative cell stress, antibody-based activation of endogenous caspase-3, and inhibition of endogenous PTP1B activity, and finally TRIM21-mediated endogenous protein degradation for potential targeted therapy. Our results thus indicate this newly developed, “mix-and-go” antibody delivery method should have broad applications in chemical biology and future drug discovery., Cell-permeant bioadaptors that can deliver native antibodies cytosolically are developed and applied to antibody-based, live-cell imaging and protein therapeutics.
- Published
- 2020
8. A Dual-Locked Activatable Phototheranostic Probe for Biomarker-Regulated Photodynamic and Photothermal Cancer Therapy
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Xin Wei, Chi Zhang, Shasha He, Jiaguo Huang, Jingsheng Huang, Si Si Liew, Ziling Zeng, Kanyi Pu, School of Chemical and Biomedical Engineering, and Lee Kong Chian School of Medicine (LKCMedicine)
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Bioengineering [Engineering] ,Photothermal Therapy ,General Chemistry ,General Medicine ,Catalysis ,Theranostic Nanomedicine ,Activatable Phototheranostic Probes ,Photochemotherapy ,Dual-Locked ,Cell Line, Tumor ,Neoplasms ,Tumor Microenvironment ,Humans ,Medicine [Science] ,Biomarkers - Abstract
Activatable phototheranostics holds promise for precision cancer treatment owing to the "turn-on" signals and therapeutic effects. However, most activatable phototheranostic probes only possess photodynamic therapy (PDT) or photothermal therapy (PTT), which suffer from poor therapeutic efficacy due to deficient cellular oxygen and complex tumor microenvironment. We herein report a dual-locked activatable phototheranostic probe that activates near-infrared fluorescence (NIRF) signals in tumor, triggers PDT in response to a tumor-periphery biomarker, and switches from PDT to PTT upon detecting a tumor-core-hypoxia biomarker. This PDT-PTT auto-regulated probe exhibits complete tumor ablation under the photoirradiation of a single laser source by producing cytotoxic singlet oxygen at the tumor periphery and generating hyperthermia at tumor-core where is too hypoxic for PDT. This dual-locked probe represents a promising molecular design approach toward precise cancer phototheranostics. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) K.P. thanks Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19; RT05/ 20), Academic Research Fund Tier 2 (MOE2018-T2-2-042; MOE-T2EP30220-0010), and A*STAR SERC AME Programmatic Fund (SERC A18A8b0059) for the financial support.
- Published
- 2022
9. Intelligentes Design von Nanomaterialien für Mitochondrien‐gerichtete Nanotherapeutika
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Lin Li, Shao Q. Yao, Xiaofei Qin, Si Si Liew, Jia Zhou, and Wei Huang
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Chemistry ,General Medicine - Published
- 2020
10. Bioinspired and biomimetic delivery platforms for cancer vaccines
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Kanyi Pu, Jun Wang, Si Si Liew, Jing Liu, and School of Chemical and Biomedical Engineering
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Materials science ,medicine.medical_treatment ,Cancer Vaccines ,Metastasis ,Immune system ,Cancer immunotherapy ,Biomimetics ,Biomimetic Materials ,Neoplasms ,medicine ,Tumor Microenvironment ,Humans ,General Materials Science ,Tumor microenvironment ,Mechanical Engineering ,Chemical engineering [Engineering] ,Cancer ,medicine.disease ,Nanomedicine ,Mechanics of Materials ,Drug delivery ,Cancer Immunotherapy ,Cancer research ,Cancer vaccine ,Immunotherapy ,Adjuvant - Abstract
Cancer vaccines aim at eliciting tumor-specific responses for the immune system to identify and eradicate malignant tumor cells while sparing the normal tissues. Furthermore, cancer vaccines can potentially induce long-term immunological memory for antitumor responses, preventing metastasis and cancer recurrence, thus presenting an attractive treatment option in cancer immunotherapy. However, clinical efficacy of cancer vaccines has remained low due to longstanding challenges, such as poor immunogenicity, immunosuppressive tumor microenvironment, tumor heterogeneity, inappropriate immune tolerance, and systemic toxicity. Recently, bioinspired materials and biomimetic technologies have emerged to play a part in reshaping the field of cancer nanomedicine. By mimicking desirable chemical and biological properties in nature, bioinspired engineering of cancer vaccine delivery platforms can effectively transport therapeutic cargos to tumor sites, amplify antigen and adjuvant bioactivities, and enable spatiotemporal control and on-demand immunoactivation. As such, integration of biomimetic designs into delivery platforms for cancer vaccines can enhance efficacy while retaining good safety profiles, which contributes to expediting the clinical translation of cancer vaccines. Recent advances in bioinspired delivery platforms for cancer vaccines, existing obstacles faced, as well as insights and future directions for the field are discussed here. Ministry of Education (MOE) K.P. thanks the Ministry of Education Singapore, Academic Research Fund Tier 1 (2019-T1-002-045 RG125/19 and RT05/20), Academic Research Fund Tier 2 (MOE2018-T2-2-042), A*STAR SERC AME Programmatic Fund (SERC A18A8b0059), the National Key R&D Program of China (2017YFA0205600), the National Natural Science Foundation of China (51633008), the Science and Technology Program of Guangzhou (007306355061), Guangdong Provincial Pearl River Talents Program (2017GC010713), the China Postdoctoral Science Foundation (2019M662933), and the Natural Science Foundation of Guangdong Province, China (No. 2021A1515010592, 2019A1515011926) for the financial support
- Published
- 2022
11. Intracellular Co-delivery of native antibody and siRNA for combination therapy by using biodegradable silica nanocapsules
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Peiyan Yuan, Fen Yang, Si Si Liew, Jiachang Yan, Xiao Dong, Jinfeng Wang, Shubo Du, Xin Mao, Liqian Gao, and Shao Q. Yao
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Biomaterials ,Drug Delivery Systems ,Nanocapsules ,Mechanics of Materials ,Biophysics ,Ceramics and Composites ,Cetuximab ,Nanoparticles ,Bioengineering ,RNA, Small Interfering ,Silicon Dioxide ,Glutathione - Abstract
Combination therapy is a promising strategy for treating multidrug-resistant (MDR) cancers. Macromolecules such as antibodies and RNAs have been successfully used for targeted therapy owing to their high specificity. However, their application as therapeutics remains limited due to membrane impermeability and poor intracellular stability. Designing drug delivery systems capable of co-administering macromolecules is therefore crucial for advancing them as therapeutics for combination therapy. Herein, by using glutathione (GSH)-responsive biodegradable silica nanocapsules (BS-NPs), we report for the first time a highly versatile nanomaterial-based strategy for co-encapsulation and intracellular co-delivery of different combinations of macromolecules (i.e., siRNA/protein, siRNA/antibody and protein/antibody). This strategy was successfully used in the intracellular co-delivery of siRNA/Cetuximab (also named Erbitux™) for combination therapy in epidermal growth factor receptor (EGFR)-overexpressing cancer cells. These BS-NPs showed good biosafety profiles and antitumor efficacy when administered in vivo, suggesting that the strategy holds potential as a novel delivery platform for combination cancer therapy.
- Published
- 2021
12. Organic Semiconducting Luminophores for Near‐Infrared Afterglow, Chemiluminescence, and Bioluminescence Imaging
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Si Si Liew, Xiaozhen Li, Kanyi Pu, Chun-Sing Lee, and Chao Yin
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Materials science ,business.industry ,Near-infrared spectroscopy ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials ,law.invention ,Afterglow ,Biomaterials ,Optical imaging ,law ,Electrochemistry ,Bioluminescence imaging ,Optoelectronics ,business ,Chemiluminescence - Published
- 2021
13. Mitochondria‐Targeting, Intracellular Delivery of Native Proteins Using Biodegradable Silica Nanoparticles
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Xiaofeng Wu, Xin Mao, Peiyan Yuan, Lin Li, Si Si Liew, and Shao Q. Yao
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Polymers ,Nanoparticle ,Mitochondrion ,010402 general chemistry ,01 natural sciences ,Catalysis ,Electron Transport Complex IV ,Silica nanoparticles ,chemistry.chemical_compound ,Drug Delivery Systems ,Organelle ,Humans ,Disulfides ,Monoamine Oxidase ,Drug Carriers ,010405 organic chemistry ,Chemistry ,Antibodies, Monoclonal ,Hep G2 Cells ,General Medicine ,General Chemistry ,Glutathione ,Biodegradation ,Silicon Dioxide ,Mitochondria ,0104 chemical sciences ,Biochemistry ,Nanoparticles ,Intracellular ,HeLa Cells ,Macromolecule - Abstract
Mitochondria are key organelles in mammalian cells whose dysfunction is linked to various diseases. Drugs targeting mitochondrial proteins provide a highly promising strategy for potential therapeutics. Methods for the delivery of small-molecule drugs to the mitochondria are available, but these are not suitable for macromolecules, such as proteins. Herein, we report the delivery of native proteins and antibodies to the mitochondria using biodegradable silica nanoparticles (BS-NPs). The modification of the nanoparticle surface with triphenylphosphonium (TPP) and cell-penetrating poly(disulfide)s (CPD) facilitated their rapid intracellular uptake with minimal endolysosomal trapping, providing sufficient time for effective mitochondrial localization followed by glutathione-triggered biodegradation and of native, functional proteins into the mitochondria.
- Published
- 2019
14. Bypassing Endocytosis: Direct Cytosolic Delivery of Proteins
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Shao Q. Yao, Lin Li, Shubo Du, and Si Si Liew
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Low protein ,Endosome ,02 engineering and technology ,Endocytosis ,01 natural sciences ,Biochemistry ,Catalysis ,Cytosol ,Drug Delivery Systems ,Colloid and Surface Chemistry ,Extracellular ,Humans ,010405 organic chemistry ,Chemistry ,Cell Membrane ,Proteins ,Biological Transport ,General Chemistry ,Protein engineering ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Transport protein ,Cell biology ,Cytoplasm ,0210 nano-technology ,Intracellular ,HeLa Cells - Abstract
Therapeutic proteins have increased dramatically in both number and frequency of use in recent years, primarily owing to advances in protein engineering. Protein therapy provides the advantages of high potency and specificity, as well as low oncogenic risks. To date, due to their inability to cross the plasma membrane into the intracellular space of mammalian cells, most therapeutic proteins can only target secreted modulators or extracellular receptors. The full potential of protein therapy is, however, being gradually realized by the development of various strategies capable of intracellular protein delivery. Notwithstanding, most of these strategies suffer from severe endosomal trapping, resulting in very low protein delivery efficiency. In this Perspective, we discuss various methods to directly transport proteins into the cell cytoplasm, thus bypassing the problems associated with endocytosis.
- Published
- 2018
15. Versatile Multiplex Endogenous RNA Detection with Simultaneous Signal Normalization Using Mesoporous Silica Nanoquenchers
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Yi Huang, Xin Mao, Peiyan Yuan, Lin Li, Shuang Wu, Shao Q. Yao, and Si Si Liew
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Messenger RNA ,Materials science ,Time Factors ,biology ,Oligonucleotide ,RNA ,Glyceraldehyde-3-Phosphate Dehydrogenases ,Biosensing Techniques ,Silicon Dioxide ,Nanostructures ,Spectrometry, Fluorescence ,Nanosensor ,Molecular beacon ,microRNA ,biology.protein ,Biophysics ,Humans ,General Materials Science ,Multiplex ,RNA, Messenger ,Porosity ,Glyceraldehyde 3-phosphate dehydrogenase ,HeLa Cells - Abstract
Detection of endogenous tumor-related RNA is vital for cancer diagnostics. Despite advancements made, live-cell RNA detection still faces numerous problems, such as low signal output and cell-to-cell variations arising from differences in probe uptake. To address these issues, we designed a versatile and highly sensitive mRNA/miRNA nanosensor featuring, for the first time, signal amplification and in-built signal normalization. Using dye-loaded mesoporous silica nanoquenchers (qMSNs) capped with target-corresponding antisense oligos (ASOs), direct fluorescence "Turn-ON" with signal amplification was achieved upon target binding. By readily varying the capping ASOs as well as cargo dyes, a suite of RNA nanosensors for multiplex target detection could be easily prepared. Further modification of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA-responsive molecular beacons (MBs) onto our nanosensor enabled dual detection of target RNA and GAPDH mRNA, allowing for target signal normalization using GAPDH as a reference. We demonstrated that this newly developed nanosensor could successfully differentiate between noncancer and cancer cells, as well as accurately monitor the relative expression levels of multiple tumor-related RNAs simultaneously in different cancer cell lines, with a high degree of specificity and sensitivity, functioning as a noninvasive "qPCR mimic" imaging tool in live cells.
- Published
- 2020
16. Intracellular delivery of therapeutic proteins through N-terminal site-specific modification
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Jie Zhang, Shao Q. Yao, Hongyan Sun, Si Si Liew, Lin Li, and Chengwu Zhang
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Models, Molecular ,RNase P ,Cell Survival ,Lysine ,Uterine Cervical Neoplasms ,Antineoplastic Agents ,Catalysis ,Drug Delivery Systems ,Materials Chemistry ,Humans ,Prodrugs ,Ribonuclease ,Cell Proliferation ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Molecular Structure ,Optical Imaging ,Metals and Alloys ,General Chemistry ,Ribonuclease, Pancreatic ,Prodrug ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Cytosol ,chemistry ,Biochemistry ,Ceramics and Composites ,biology.protein ,Female ,Antibody ,Drug Screening Assays, Antitumor ,Reactive Oxygen Species ,Intracellular ,HeLa Cells - Abstract
A versatile strategy for the intracellular delivery of functional proteins/antibodies was developed using N-terminal site-specific modification. Adopting orthogonal dual-labeling strategies, a cell-permeable RNase A prodrug was designed complementing N-terminal site-specific modification with lysine labeling. Upon successful cytosolic uptake, the prodrug showed reactive oxygen species (ROS)-dependent targeted cancer therapy.
- Published
- 2020
17. Discovery of dual GyrB/ParE inhibitors active against Gram-negative bacteria
- Author
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John I. Manchester, Vishal Pendharkar, Thomas H. Keller, Yvonne Tan, Shi Hua Ang, Si Si Liew, Sum Wai Eldwin Tan, Zhi Ying Poh, Yin Sze Joyner Wong, Kanda Sangthongpitag, Fui Mee Ng, Weiling Wang, Jeffrey Hill, Joseph Cherian, Yun Xuan Wong, Gregory S. Basarab, Soo Yei Ho, and Anders Poulsen
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DNA Topoisomerase IV ,0301 basic medicine ,Gram-negative bacteria ,Topoisomerase Inhibitors ,030106 microbiology ,Microbial Sensitivity Tests ,DNA gyrase ,Structure-Activity Relationship ,03 medical and health sciences ,Drug Discovery ,Escherichia coli ,Pharmacology ,Dose-Response Relationship, Drug ,Molecular Structure ,biology ,Chemistry ,Organic Chemistry ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Anti-Bacterial Agents ,Streptococcus pneumoniae ,030104 developmental biology ,Membrane ,Biochemistry ,DNA Gyrase ,Permeability (electromagnetism) ,Efflux ,Bacteria - Abstract
Even though many GyrB and ParE inhibitors have been reported in the literature, few possess activity against Gram-negative bacteria. This is primarily due to limited permeability across Gram-negative bacterial membrane as well as bacterial efflux mechanisms. Permeability of compounds across Gram-negative bacterial membranes depends on many factors including physicochemical properties of the inhibitors. Herein, we show the optimization of pyridylureas leading to compounds with potent activity against Gram-negative bacterial species such as P.aeruginosa, E.coli and A.baumannii.
- Published
- 2018
18. Smart Design of Nanomaterials for Mitochondria-Targeted Nanotherapeutics
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Wei Huang, Shao Q. Yao, Xiaofei Qin, Jia Zhou, Si Si Liew, and Lin Li
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Target site ,Computer science ,Humans ,Nanoparticles ,Nanotechnology ,General Chemistry ,Nanocarriers ,Catalysis ,Organelle localization ,Mitochondria targeted ,Mitochondria ,Nanostructures - Abstract
Mitochondria are the powerhouse of cells. They are vital organelles that maintain cellular function and metabolism. Dysfunction of mitochondria results in various diseases with a great diversity of clinical appearances. In the past, strategies have been developed for fabricating subcellular-targeting drug-delivery nanocarriers, enabling cellular internalization and subsequent organelle localization. Of late, innovative strategies have emerged for the smart design of multifunctional nanocarriers. Hierarchical targeting enables nanocarriers to evade and overcome various barriers encountered upon in vivo administration to reach the organelle with good bioavailability. Stimuli-responsive nanocarriers allow controlled release of therapeutics to occur at the desired target site. Synergistic therapy can be achieved using a combination of approaches such as chemotherapy, gene and phototherapy. In this Review, we survey the field for recent developments and strategies used in the smart design of nanocarriers for mitochondria-targeted therapeutics. Existing challenges and unexplored therapeutic opportunities are also highlighted and discussed to inspire the next generation of mitochondrial-targeting nanotherapeutics.
- Published
- 2019
19. A Vinyl Sulfone-Based Fluorogenic Probe Capable of Selective Labeling of PHGDH in Live Mammalian Cells
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Jun-Seok Lee, Jiaqi Fu, Sijun Pan, Si Si Liew, Shao Q. Yao, Danyang Wang, and Se-Young Jang
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Dehydrogenase ,010402 general chemistry ,01 natural sciences ,Fluorescence ,Catalysis ,Live cell imaging ,Chlorocebus aethiops ,Animals ,Humans ,Moiety ,Organic chemistry ,Sulfones ,Phosphoglycerate dehydrogenase ,Phosphoglycerate Dehydrogenase ,Fluorescent Dyes ,COS cells ,Molecular Structure ,Chemistry ,010405 organic chemistry ,fungi ,Hep G2 Cells ,General Chemistry ,General Medicine ,Small molecule ,In vitro ,0104 chemical sciences ,Molecular Docking Simulation ,Spectrometry, Fluorescence ,Biochemistry ,COS Cells ,MCF-7 Cells - Abstract
Chemical probes are powerful tools for interrogating small molecule-target interactions. With additional fluorescence Turn-ON functionality, such probes might enable direct measurements of target engagement in live mammalian cells. DNS-pE (and its terminal alkyne-containing version DNS-pE2) is the first small molecule that can selectively label endogenous 3-phosphoglycerate dehydrogenase (PHGDH) from various mammalian cells. Endowed with an electrophilic vinyl sulfone moiety that possesses fluorescence-quenching properties, DNS-pE/DNS-pE2 became highly fluorescent only upon irreversible covalent modification of PHGDH. With an inhibitory property (in vitro Ki =7.4 μm) comparable to that of known PHGDH inhibitors, our probes thus offer a promising approach to simultaneously image endogenous PHGDH activities and study its target engagement in live-cell settings.
- Published
- 2017
20. A Suite of 'Minimalist' Photo-Crosslinkers for Live-Cell Imaging and Chemical Proteomics: Case Study with BRD4 Inhibitors
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Sijun Pan, Se-Young Jang, Si Si Liew, Zhengqiu Li, Shao Q. Yao, Jun-Seok Lee, and Danyang Wang
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Proteomics ,BRD4 ,010405 organic chemistry ,Chemistry ,Nuclear Proteins ,Cell Cycle Proteins ,General Medicine ,General Chemistry ,Photochemical Processes ,010402 general chemistry ,01 natural sciences ,Small molecule ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Cross-Linking Reagents ,Biochemistry ,Live cell imaging ,Stable isotope labeling by amino acids in cell culture ,Diazirine ,Humans ,Bioorthogonal chemistry ,Transcription Factors - Abstract
Affinity-based probes (AfBPs) provide a powerful tool for large-scale chemoproteomic studies of drug-target interactions. The development of high-quality probes capable of recapitulating genuine drug-target engagement, however, could be challenging. "Minimalist" photo-crosslinkers, which contain an alkyl diazirine group and a chemically tractable tag, could alleviate such challenges, but few are currently available. Herein, we have developed new alkyl diazirine-containing photo-crosslinkers with different bioorthogonal tags. They were subsequently used to create a suite of AfBPs based on GW841819X (a small molecule inhibitor of BRD4). Through in vitro and in situ studies under conditions that emulated native drug-target interactions, we have obtained better insights into how a tag might affect the probe's performance. Finally, SILAC-based chemoproteomic studies have led to the discovery of a novel off-target, APEX1. Further studies showed GW841819X binds to APEX1 and caused up-regulation of endogenous DNMT1 expression under normoxia conditions.
- Published
- 2017
21. A chemoselective cleavable fluorescence turn-ON linker for proteomic studies
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Shubo Du, Se-Young Jang, Shao Q. Yao, Si Si Liew, Sijun Pan, Jingyan Ge, and Jun-Seok Lee
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Proteomics ,Proteome ,010402 general chemistry ,Cleavage (embryo) ,01 natural sciences ,Fluorescence ,Catalysis ,Turn (biochemistry) ,Materials Chemistry ,Organic chemistry ,Molecule ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Metals and Alloys ,General Chemistry ,Combinatorial chemistry ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Proteome profiling ,Ceramics and Composites ,Linker - Abstract
We have developed a trifunctional cleavable fluorescence turn-ON linker for chemoproteomic applications. This novel linker, which became highly fluorescent only upon cleavage of the azo bond, was successfully used for in situ proteome profiling/target identification and studies on newly synthesised proteomes.
- Published
- 2017
22. Renal-Clearable Molecular Probe for Near-Infrared Fluorescence Imaging and Urinalysis of SARS-CoV-2.
- Author
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Si Si Liew, Ziling Zeng, Penghui Cheng, Shasha He, Chi Zhang, and Kanyi Pu
- Published
- 2021
- Full Text
- View/download PDF
23. Discovery of Irreversible Inhibitors Targeting Histone Methyltransferase, SMYD3
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Jeffrey Hill, Joma Joy, Grace Lin, Nurul Dinie, Justina Fulwood, Sin Yin Chew, Xiaoying Koh-Stenta, Sugunavathi Sepramaniam, Xin Hui Chew, Rong Li, Melgious Jin Yan Ang, May Ann Lee, Alex Matter, Weixuan Yu, Zhiyuan Ke, Anna Ngo, Hwa Hwa Chung, Susmitha Vuddagiri, Kanda Sangthongpitag, Klement Foo, Vithya Manoharan, C. S. Brian Chia, Sravanthy Manesh, Esther H. Q. Ong, Nithya Baburajendran, Chuhui Huang, Zekui Perlyn Kwek, John Liang Kuan Wee, Yun Shan Chew, Priya Retna, Thomas H. Keller, Anders Poulsen, Si Si Liew, Choon Bing Low, and Vishal Pendharkar
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chemistry.chemical_classification ,Methyltransferase ,Chemistry ,Organic Chemistry ,Biochemistry ,Cell biology ,3D cell culture ,Enzyme ,Mechanism of action ,Covalent bond ,Histone methyltransferase ,Drug Discovery ,medicine ,Epigenetics ,medicine.symptom ,Transferase inhibitor - Abstract
[Image: see text] SMYD3 is a histone methyltransferase that regulates gene transcription, and its overexpression is associated with multiple human cancers. A novel class of tetrahydroacridine compounds which inhibit SMYD3 through a covalent mechanism of action is identified. Optimization of these irreversible inhibitors resulted in the discovery of 4-chloroquinolines, a new class of covalent warheads. Tool compound 29 exhibits high potency by inhibiting SMYD3′s enzymatic activity and showing antiproliferative activity against HepG2 in 3D cell culture. Our findings suggest that covalent inhibition of SMYD3 may have an impact on SMYD3 biology by affecting expression levels, and this warrants further exploration.
- Published
- 2019
24. Correction to 'Discovery of Irreversible Inhibitors Targeting Histone Methyltransferase, SMYD3'
- Author
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Sugunavathi Sepramaniam, Thomas H. Keller, Alex Matter, Xiaoying Koh-Stenta, May Ann Lee, Nurul Dinie, Anders Poulsen, Justina Fulwood, Weixuan Yu, Anna Ngo, Grace Lin, Sin Yin Chew, Xin Hui Chew, Joma Joy, Melgious Jin Yan Ang, Priya Retna, Kanda Sangthongpitag, Nithya Baburajendran, John Liang Kuan Wee, Klement Foo, Jeffrey Hill, Vithya Manoharan, Zekui Perlyn Kwek, Esther H. Q. Ong, Zhiyuan Ke, Rong Li, Chuhui Huang, Hwa Hwa Chung, C. S. Brian Chia, Yun Shan Chew, Susmitha Vuddagiri, Sravanthy Manesh, Vishal Pendharkar, Si Si Liew, and Choon Bing Low
- Subjects
Chemistry ,Histone methyltransferase ,Organic Chemistry ,Drug Discovery ,Biochemistry ,Cell biology - Published
- 2019
Catalog
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