Aptamers and Their Potential in Site-Specific Nanotherapy Against Hepatocellular Carcinoma

Globally, hepatocellular carcinoma (HCC) is one of the most devastating neoplasia and has a remarkably high mortality rate. Furthermore, the long latent period associated with HCC lends the diagnosis at the intermediate or advanced stages where the chemotherapy is the solitary therapeutic intervention. The responsiveness of HCC towards conventional chemotherapeutic agents is notably poor due to multiple factors. Among them, multiple drug resistance, reduced drug concentration at the tumor site, quicker clearance, and non-specific distribution are the prime causes leading to remarkably high off-target toxicity and mortality. More importantly, the approval of several multikinase inhibitors (MKIs) by the United States Food and Drug Administration (FDA) for the treatment of HCC as targeted therapeutics has been found to be inadequate to make a notable impact on survival. Therefore, ligand-based targeted therapeutics capable of delivering the therapeutic modality specifically into neoplastic hepatocytes have been explored extensively by researchers worldwide. Among the plethora of HCC-targeting ligands, aptamer-based targeted therapeutics in HCC have gained significant momentum compared to others due to some signature characteristics of aptamer, namely non-immunogenicity, low cost, non-toxicity, thermostability, simpler manufacturing, and high suitability for chemical modification. Despite their enormous potential, aptamer-based targeted therapeutics are still in infancy and require smarter thinking and quick translation from e-clinical to clinical application. Thus, the fundamental focus of the book chapter is to highlight promising features of aptamers, their production, chemical modification, mechanism of action, and finally, detailed emphasis has been given on the overall scenario of aptamer-based targeted therapeutics in HCC.