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  • Herein we further established a

    2019-11-29

    Herein, we further established a dynamic DNA self-assembly activated hemin-mimetic enzymes system by embedding DNA-hemin into an entropy-driven DNA-assembly for fluorescent biosensing. The entropy-driven dynamic DNA-assembly is one of the toehold-mediated isothermal strand displacement reactions, which is driven forward by increases in the Diperodon HCl of the system and possesses the advantages of rapid and effective amplification performance, high thermostability, flexible sequence design and decreased reversible conversion [30,31]. Hence, we utilize this strategy as an efficient dynamic DNA self-assembly to activate the DNA-hemin mimetic enzymes for enzyme-free signal amplification and biosensing. Hemin dimmers with suppressed catalytic activity were firstly formed due to the complementary of DNA strands. In the presence of target DNA, the dynamic DNA-assembly amplification reaction was initiated, along with the separation of hemin dimmers into monomers to modulate the DNA-hemin enzyme activity. Once the catalytic activity of hemin-mimetic enzymes was activated, the substrate tyramine can be catalyzed into fluorescent dityramine, producing a dramatically enhanced fluorescence signal. In this system, the DNA-hemin not only was utilized as the module for dynamic DNA-assembly but also as the tunable mimetic enzyme, providing a simple, fast and enzyme-free signal amplification strategy. The proposed strategy was applied to detect the specific pathogenic gene of Group B Streptococci (GenBank Accession no.1012782) and small molecule cocaine, proving its simplicity, practicability for versatile fluorescent biosensing.
    Experimental
    Results and discussion
    Conclusion
    Acknowledgements This work was funded by the National Natural Science Foundation of China (81572080, 81873972and81873980), the National Science and Technology Major Project of the Ministry of Science and Technology of China (2018ZX10732202), the Natural Science Foundation Project of Chongqing (cstc2015shmszx120086) and the Training Program for Advanced Young Medical Personnel of Chongqing (2017HBRC003).
    Introduction Past century has witnessed a tremendous increase in life expectancy of the human population, achieved through an overall higher quality of life. One of the major developments and factors contributing to this achievement is the progress in medicinal chemistry, from identification of numerous new drug targets, [1], [2], [3] to the development of high throughput techniques [4] and fragment-based tools [5] for identification of pharmaceutical leads, to synthetic methodologies applied for optimization of drug candidates with the view of improved pharmacokinetics (PK) [6]. However, it remains a great challenge to deliver the drugs to their nominated site of action. Indeed, producing a molecular entity with a desired and even a highly favorable pharmacodynamics effect has become a routine accomplishment of medicinal chemistry. Yet the success rate associated with progression from lab to the clinic remains very low [7]. In large part, translational research for novel drug candidates is troublesome due to systemic distribution of the drug and ensuing side effects. It is understood that delivering the drugs specifically to their site of action is key to higher therapeutic benefits. Indeed, successful tools such as antibody-drug conjugates (ADC) are entering the market and as such represent a major success of medicinal chemistry [8]. However, in-depth analysis of ADC reveals that even with the use of antibodies, arguably the ultimate targeting tools designed by nature itself, a mere 1–2% Diperodon HCl of the payload is reaching the nominated target, [8] leaving much room for improvement. Site-specific drug delivery using therapeutic implants offers significant advantages over systemic administration of drugs. Admittedly, pill-based drug administration is more patient-compliant, non-invasive, and most convenient in the majority of cases of drug delivery. However, localized drug delivery is an ultimate tool to achieve the feed of the nominated therapeutic directly to the desired cells and tissues. Successful examples of these tools include cardiovascular implants produced to locally feed anti-proliferative drugs and thus minimize the detrimental overgrowth of the stents with myoblasts [9]. Drug releasing implants based on degradable organic polymers release anticancer drugs locally, when the implants are placed through surgery at the site of brain tumor [10]. Drug eluting beads are successful in delivering drugs to the non-resectable hepatocellular carcinomas [11]. These and other examples of localized drug delivery illustrate the advantages of site-specific drug delivery but also highlight its limitations. Specifically, by design, implants are engineered to perform their nominated function autonomously, but in doing so, these materials offer no control over drug elution and neither patient nor doctors can change the drug prescription from A to B, double the dose of the drug, stop drug elution, or achieve drug elution on demand. These opportunities are highly desired but to date have hardly been achieved.