Click Chemistry-Based Nanomaterial Modification for Cancer Targeting: A Review

Chemical and biological orthogonal reactions involving click chemistry continue to be a prominent area of interest in biomedical research. Click chemistry, as a linking reaction, effectively connects diverse small molecular units to generate large molecules with specific structures and functions. This reaction finds widespread application in modifying the surfaces of nanoparticles. Traditional organic chemistry often encounters challenges in synthesizing carbon heteroatom bonds, often accompanied by numerous side reactions. Moreover, the limited availability of chemical groups on nanoparticle surfaces significantly restricts their modification through conventional organic reactions. However, the development of click chemistry has triumphed over these hurdles, ensuring that complex organic reactions no longer impede nanoparticle surface modification research. These high-performance chemical reactions possess characteristics that are often absent in the current biological environment, including high selectivity, rapid reaction rates, and excellent biocompatibility. The utilization of click chemistry has greatly propelled the application of nanoparticles in the realm of tumor treatment. Increasingly, tumor-targeting molecules are being conjugated to the surfaces of nanoparticles through click reactions. Furthermore, bioorthogonal reactions derived from click chemistry are emerging as a trending topic in contemporary tumor treatment. These trends are becoming increasingly apparent in recent reports, garnering greater attention to click chemistry and bioorthogonal reactions within the field of nanomedicine engineering. In this review, we elucidate the potential for modifications of nanomaterials using click chemistry, with a particular focus on its role in targeted cancer treatment. Additionally, we summarize the existing challenges and future opportunities in this domain.