Chapter 9 - Chemical linkers: Potential approach to target tumor

Abstract

Tumor-targeting chemotherapeutics are promising for improving cancer treatment efficacy and minimizing side effects. Among the different approaches of tumor targeting, a chemical linker-based approach has been investigated widely. In this approach, two fragments (i.e., drug and carrier) are bound together using different chemical linkers that can be cleaved by tumor-specific enzymes or other stimulus to release the payload at the tumor site. The success of chemical linker-mediated tumor targeting depends upon the perfect balance between the linker’s stability in plasma and its selective cleavage at the tumor site. Both cleavable and noncleavable linkers have been utilized for tumor targeting and have their own pros and cons. Cleavable linkers are more prevalent and cleaved by pH, enzymes, reducing agents, photo-irradiation, exogenous stimuli, and so on. Noncleavable linkers are more dependent on the biology of the target cells than cleavable linkers and avoid nonspecific release of the drug. Nowadays, antibody-drug conjugates utilizing both cleavable and noncleavable linkers have been established as a major class of therapeutics for the clinical treatment of cancer. This chapter examines in detail linkers that have been widely investigated in developing drug conjugates for tumor targeting.