Abstract

Click chemistry has great potential for use in binding between nucleic acids, lipids, proteins, and other molecules, and has been used in many research fields because of its beneficial characteristics, including high yield, high specificity, and simplicity. The recent development of copper-free and less cytotoxic click chemistry reactions has allowed for the application of click chemistry to the field of medicine. Moreover, metabolic glycoengineering allows for the direct modification of living cells with substrates for click chemistry either in vitro or in vivo. As such, click chemistry has become a powerful tool for cell transplantation and drug delivery. In this review, we describe some applications of click chemistry for cell engineering in cell transplantation and for drug delivery in the diagnosis and treatment of diseases.

Highlights

  • Click chemistry is a term that was first proposed by Sharpless et al in 2001

  • We describe the applications of click chemistry for cell engineering and drug delivery systems for the diagnosis and treatment of diseases

  • The authors demonstrated that the combination of metabolic glycoengineering and the strain-promoted [3 + 2] azide-alkyne cycloaddition (SPAAC) reaction allowed for the modification of mesenchymal stem cells (MSCs) with CNPs in a short reaction time, and that CNP-modified MSCs could be tracked over the long-term. These results indicate that the combination of metabolic glycoengineering and the SPAAC reaction may be a good tool to add anti-cancer functions to MSCs by modifying MSCs with anticancer agent-loaded CNPs

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Summary

Introduction

Click chemistry is a term that was first proposed by Sharpless et al in 2001. The characteristics of click chemistry include a high yield, a wide scope, less cytotoxic byproducts, a high stereospecificity, and a simple reaction [1]. The strain-promoted [3 + 2] azide-alkyne cycloaddition (SPAAC) reaction, which is a new type copper-free click chemistry developed by Bertozzi et al in 2004, has brought about the successful application of click reactions to living cells without copper-induced cytotoxicity They reported that cyclooctyne (OCT) reacted with azide under physiological conditions without copper catalysis (Scheme 1B) [4,5]. Other researchers vinylboronic acid [18], which react withreporters tetrazines under physiological conditions, and have have developed bioorthogonal chemical of (Tz) the iEDDA reaction, including norbornene [14], demonstrated their usefulness for cell labeling with fluorophore and functional molecules. Azide groups on cell surfaces and 2 summarize the non-toxic dose ranges of the reagents reported in in vitro and in vivo studies after metabolic glycoengineering gradually disappear due to the hydrolysis of glycans by neuraminidase using click chemistry and metabolic glycoengineering. We describe the applications of click chemistry for cell engineering and drug the diagnosis and treatment of diseases

Schematic illustration cell labeling via metabolic
Click Chemistry as a Tool for Cell Engineering in Cell Transplantation
Click Chemistry as a Tracking Tool for Transplanted Cells
ManNAz transplanted
Click Chemistry as a Tool for Cell-Based Drug Delivery
Schematic
Applications of Click Chemistry for the Formation of Cell Complexes
Tumor-Specific Labeling with Azide Groups
64 Cu-NOTA-PEG
Tumor-Targeting Delivery by Click Chemistry for Cancer Therapy
Application of iEDDA Reaction for Tumor-Specific Delivery
Conclusions
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