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Fluorescent molecular probes are very powerful tools that have been generally applied in cell imaging in the research fields of biology, pathology, pharmacology, biochemistry, and medical science. In the last couple of decades, nu...
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Fluorescent molecular probes are very powerful tools that have been generally applied in cell imaging in the research fields of biology, pathology, pharmacology, biochemistry, and medical science. In the last couple of decades, numerous molecular probes endowed with high specificity to particular organelles have been designed to illustrate intracellular images in more detail at the subcellular level. Nowadays, the development of cell biology has enabled the investigation process to go deeply into cells, even at the molecular level. Therefore, probes that can sketch a particular organelle’s location while responding to certain parameters to evaluate intracellular bioprocesses are under urgent demand. It is significant to understand the basic ideas of organelle properties, as well as the vital substances related to each unique organelle, for the design of probes with high specificity and efficiency. In this review, we summarize representative multifunctional fluorescent molecular probes developed in the last decade. We focus on probes that can specially target nuclei, mitochondria, endoplasmic reticulums, and lysosomes. In each section, we first briefly introduce the significance and properties of different organelles. We then discuss how probes are designed to make them highly organelle-specific. Finally, we also consider how probes are constructed to endow them with additional functions to recognize particular physical/chemical signals of targeted organelles. Moreover, a perspective on the challenges in future applications of highly specific molecular probes in cell imaging is also proposed. We hope that this review can provide researchers with additional conceptual information about developing probes for cell imaging, assisting scientists interested in molecular biology, cell biology, and biochemistry to accelerate their scientific studies.
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In recent years, DNA has been widely noted as a kind of material that can be used to construct building blocks for biosensing, in vivo imaging, drug development, and disease therapy because of its advantages of good biocompatibili...
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In recent years, DNA has been widely noted as a kind of material that can be used to construct building blocks for biosensing, in vivo imaging, drug development, and disease therapy because of its advantages of good biocompatibility and programmable properties. However, traditional DNA-based sensing processes are mostly achieved by random diffusion of free DNA probes, which were restricted by limited dynamics and relatively low efficiency. Moreover, in the application of biosystems, single-stranded DNA probes face challenges such as being difficult to internalize into cells and being easily decomposed in the cellular microenvironment. To overcome the above limitations, DNA nanostructure-based probes have attracted intense attention. This kind of probe showed a series of advantages compared to the conventional ones, including increased biostability, enhanced cell internalization efficiency, accelerated reaction rate, and amplified signal output, and thus improved in vitro and in vivo applications. Therefore, reviewing and summarizing the important roles of DNA nanostructures in improving biosensor design is very necessary for the development of DNA nanotechnology and its applications in biology and pharmacology. In this perspective, DNA nanostructure-based probes are reviewed and summarized from several aspects: probe classification according to the dimensions of DNA nanostructures (one, two, and three-dimensional nanostructures), the common connection modes between nucleic acid probes and DNA nanostructures, and the most important advantages of DNA self-assembled nanostructures in the applications of biosensing, imaging analysis, cell assembly, cell capture, and theranostics. Finally, the challenges and prospects for the future development of DNA nanostructure-based nucleic acid probes are also discussed.
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Cell-cell aggregation is one of the most well-known modes of intercellular communication. The aggregation also plays a vital role in the formation of multicellularity, thus manipulating the growth and development of organisms. In ...
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Cell-cell aggregation is one of the most well-known modes of intercellular communication. The aggregation also plays a vital role in the formation of multicellularity, thus manipulating the growth and development of organisms. In the past decades, cell-cell aggregation-related bioprocesses and molecular mechanisms have attracted enormous interest from scientists in biology, and bioengineering. People have developed a series of strategies to artificially regulate cell-cell aggregation through chemical-biological approaches. To date, not only the chemical reagents such as coordination compounds and polymers but also the biomacromolecules such as proteins and nucleic acids, are employed as the "cell glue" to achieve the control of the cell aggregation. So it is meaningful to review the recent advances of the chemical-biological approaches in cell-cell aggregation manipulation. In this review, we discuss the mechanisms and features of recently developed strategies to control cell-cell aggregation. We introduce molecules and designs relying on chemical reactions and biological conjugations respectively, and talk about their advantages and suitable applications. A perspective on the challenges in future applications in cell manipulation and cell-based therapy is also proposed. We expect this review could inspire innovative work on manipulating cell-cell aggregation and further modulate cell-cell interactions in the research of bio/chemical fields.
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This paper proposes a bat robot mechanism and investigates the kinematics of flying process. After observing the flight of bats for a long period of time and analysing its flying kinematics, a bionic robot was synthesised based on...
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This paper proposes a bat robot mechanism and investigates the kinematics of flying process. After observing the flight of bats for a long period of time and analysing its flying kinematics, a bionic robot was synthesised based on the bat structure to realise the deploying and flapping movements of the double membranous wings. With screw theory, the primary motion of the membranous wings was checked and six actuators were selected for controlling the flapping flight of the bat robot collaboratively. The structure is optimised by a bench test. A method is presented to measure the force output of the bat robot.
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Ligands that can interact specifically with telomeric multimeric G-quadruplexes could be developed as promising anticancer drugs with few side effects related to other G-quadruplex-forming regions. In this paper, a new cationic po...
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Ligands that can interact specifically with telomeric multimeric G-quadruplexes could be developed as promising anticancer drugs with few side effects related to other G-quadruplex-forming regions. In this paper, a new cationic porphyrin derivative, m-TMPipEOPP, was synthesized and characterized. Its multimeric G-quadruplex recognition specificity under molecular crowding conditions was compared to its isomer p-TMPipEOPP. The slight structural difference accounts for different multimeric G-quadruplex recognition specificity for the two isomers. p-TMPipEOPP can barely discriminate between multimeric and monomeric G-quadruplexes. By contrast, m-TMPipEOPP can bind with multimeric but not with monomeric G-quadruplexes. p-TMPipEOPP might bind to multimeric G-quadruplexes by two modes: sandwich-like end-stacking mode and pocket-dependent intercalative mode. Increasing the pocket size between adjacent two G-quadruplex uints is beneficial for the latter mode. m-TMPipEOPP might bind to multimeric G-quadruplexes by a side binding mode, which confers m-TMPipEOPP with higher multimeric G-quadruplex recognition specificity compared to p-TMPipEOPP. m-TMPipEOPP increases the stability of multimeric G-quadruplex under both dilute and molecular crowding conditions but its G-quadruplex-stabilizing ability is a little weaker than p-TMPipEOPP. These results provide important information for the design of highly specific multimeric G-quadruplex ligands. Another interesting finding is that pocket size is an important factor in determining the stability of multimeric G-quadruplexes.
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Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we repor...
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Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we reported a new specific G-quadruplex-probing technique—resonance light scattering (RLS)-based ratiometric recognition. To achieve the RLS probing of G-quadruplexes in the important physiological pH range of 7.4-6.0, four water soluble cationic porphyrin derivatives, including an unreported octa-cationic porphyrin, with large side arm substituents were synthesized and developed as RLS probes. These RLS probes were demonstrated to work well for ratiometric recognition of G-quadruplexes with high specificity against single- and double-stranded DNAs, including long double-stranded ones. The working mechanism was speculated to be based on the RLS signal changes caused by porphyrin protonation that was promoted by the end-stacking of porphyrins on G-quadruplexes. This work adds an important member in G-quadruplex probe family, thus providing a useful tool for studies on G-quadruplex-related events concerning G-quadruplex formation, destruction and changes in size, shape and aggregation. As a proof-of-concept example of applications, the RLS probes were demonstrated to work well for label-free and sequence-specific sensing of microRNA. This work also provides a simple and useful way for the preparation of cationic porphyrins with high charges.
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Ligands targeting telomeric G-quadruplexs are considered good candidates for anticancer drugs. However, current studies on G-quadruplex ligands focus exclusively on the interactions of ligands and monomeric G-quadruplexes under di...
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Ligands targeting telomeric G-quadruplexs are considered good candidates for anticancer drugs. However, current studies on G-quadruplex ligands focus exclusively on the interactions of ligands and monomeric G-quadruplexes under dilute conditions. Living cells are crowded with biomacromolecules, and the ～200-nucleotide G-rich single-stranded overhang of human telomeric DNA has the potential to fold into multimeric G-quadruplex structures containing several G-quadruplex units. Studies on interactions between ligands and multimeric G-quadruplexes under molecular crowding conditions could provide a new route for screening specific telomeric G-quadruplex-targeting ligands. Herein, TMPipEOPP, a cationic porphyrin derivative designed by us, was demonstrated as a promising multimeric telomeric G-quadruplex ligand under molecular crowding conditions. It could highly specifically recognize G-quadruplexes. It could also promote the formation of G-quadruplexes and stabilize them. Detailed studies showed that TMPipEOPP interacted with monomeric G-quadruplexes in sandwich-like end-stacking mode of quadruplex/TMPipEOPP/quadruplex and interacted with multimeric human telomeric G-quadruplexes by intercalating into the pocket between two adjacent G-quadruplex units. The pocket size greatly affected TMPipEOPP binding. A larger pocket was advantageous for the intercalation of TMPipEOPP. This work provides new insights into the ligand-binding properties of multimeric G-quadruplexes under molecular crowding conditions and introduces a new route for screening anticancer drugs targeting telomeric G-quadruplexes.
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摘要 :
Ligands targeting telomeric G-quadruplexs are considered good candidates for anticancer drugs. However, current studies on G-quadruplex ligands focus exclusively on the interactions of ligands and monomeric G-quadruplexes under di...
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Ligands targeting telomeric G-quadruplexs are considered good candidates for anticancer drugs. However, current studies on G-quadruplex ligands focus exclusively on the interactions of ligands and monomeric G-quadruplexes under dilute conditions. Living cells are crowded with biomacromolecules, and the ~200-nucleotide G-rich single-stranded overhang of human telomeric DNA has the potential to fold into multimeric G-quadruplex structures containing several G-quadruplex units. Studies on interactions between ligands and multimeric G-quadruplexes under molecular crowding conditions could provide a new route for screening specific telomeric G-quadruplex-targeting ligands. Herein, TMPipEOPP, a cationic porphyrin derivative designed by us, was demonstrated as a promising multimeric telomeric G-quadruplex ligand under molecular crowding conditions. It could highly specifically recognize G-quadruplexes. It could also promote the formation of G-quadruplexes and stabilize them. Detailed studies showed that TMPipEOPP interacted with monomeric G-quadruplexes in sandwich-like end-stacking mode of quadruplex/TMPipEOPP/quadruplex and interacted with multimeric human telomeric G-quadruplexes by intercalating into the pocket between two adjacent G-quadruplex units. The pocket size greatly affected TMPipEOPP binding. A larger pocket was advantageous for the intercalation of TMPipEOPP. This work provides new insights into the ligand-binding properties of multimeric G-quadruplexes under molecular crowding conditionsand introduces a new route for screening anticancer drugs targeting telomeric G-quadruplexes.
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The separation and detection of circulating tumor cells (CTCs) have a significant impact on clinical diagnosis and treatment by providing a predictive diagnosis of primary tumors and tumor metastasis. But the responsive release an...
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The separation and detection of circulating tumor cells (CTCs) have a significant impact on clinical diagnosis and treatment by providing a predictive diagnosis of primary tumors and tumor metastasis. But the responsive release and downstream analysis of live CTCs will provide more valuable information about molecular markers and functional properties. To this end, specific capture and controllable release methods, which can achieve the highly efficient enrichment of CTCs with strong viability, are urgently needed. DNA networks create a flexible, semi-wet three-dimensional (3D) microenvironment for cell culture, and have the potential to minimize the loss of cell viability and molecular integrity. More importantly, responsive DNA networks can be reasonably designed as smart sensors and devices to change shape, color, disassemble, and giving back to external stimuli. Here, a strategy for specifically collecting cells using a dual-aptamer DNA network is designed. The proposed strategy enables effective capture, 3D encapsulation, and responsive release of CTCs with strong viability, which can be used for downstream analysis of live cells. The programmability of CRISPR/Cas12a, a powerful toolbox for genome editing, is used to activate the responsive release of captured CTCs from the DNA network. After activation by a specified double-strand DNA (dsDNA) input, CRISPR/Cas12a cleaves the single-stranded DNA regions in the network, resulting in molecular to macroscopic changes in the network. Accompanied by the deconstruction of the DNA network into fragments, controllable cell release is achieved. The viability of released CTCs is well maintained and downstream cell analysis can be performed. This strategy uses the enzymatic properties of CRISPR/Cas12a to design a platform to improve the programmability and versatility of the DNA network, providing a powerful and effective method for capturing and releasing CTCs from complex physiological samples.
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A water soluble cationic porphyrin derivative 5,10,15,20-tetra-{4-[3-(1-methyl-1-piperidinyl) propoxy]phenyl}porphyrin (TMPipPrOPP), which showed attractive pH-dependent optical responses to G-quadruplexes, was synthesized and cha...
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A water soluble cationic porphyrin derivative 5,10,15,20-tetra-{4-[3-(1-methyl-1-piperidinyl) propoxy]phenyl}porphyrin (TMPipPrOPP), which showed attractive pH-dependent optical responses to G-quadruplexes, was synthesized and characterized. Under molecular crowding conditions, a stable TMPipPrOPP/G-quadruplex complex was formed in acidic pH range. Alkalization of the system to neutral and basic pH caused destruction of the complex due to reduced electrostatic interactions. The formation and destruction of the TMPipPrOPP/G-quadruplex complex was reversibly adjusted by pH, accompanied by repeated on-off switching of the colorimetric and fluorescent responses of TMPipPrOPP to G-quadruplexes. In comparison, no optical responses were observed for single-stranded, duplex and i-motif DNAs in the tested pH range (5.0-8.5). Besides highlighting the importance of designing novel drugs targeting G-quadruplexes in specific genome regions, this work may also provide a useful tool for G-quadruplex-based biosensing and nanomachine construction. One example is the design of colorimetric and fluorescent sensors for ratiometric pH-sensing. The proposed sensing platform can be used not only for highly sensitive pH-sensing in a narrow biological pH range, but also for pH detection in a broad range. Another example is the construction of DNA-based dual-output all-optical molecular logic gates that can perform basic AND, NAND, OR, NOR, INHIBIT and IMPLICATION logic operations.
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