Aptamers and nanobodies as alternatives to antibodies for ligand-targeted drug delivery in cancer

Targeted drug delivery (TDD) is the selective delivery of a therapeutic agent specifically to the site of action to avoid adverse effects and systemic toxicity and to reduce the dose required. Ligand TDD or active TDD involves using a ligand-drug conjugate comprising a targeting ligand linked to an active drug moiety that can either be free or encapsulated within a nanocarrier (NC). Aptamers are single-stranded oligonucleotides that bind to specific biomacromolecules because of their 3D conformation. Nanobodies are the variable domains of unique heavy chain-only antibodies (HcAbs) produced by animals of the Camelidae family. Both these types of ligand are smaller than antibodies and have been used to efficiently target drugs to particular tissues or cells. In this review, we describe the applications of aptamers and nanobodies as ligands for TDD, their advantages and disadvantages compared with antibodies, and the various modalities for targeting cancers using these ligands. Teaser: Aptamers and nanobodies are macromolecular ligands that can actively chaperone drug molecules to particular cancerous cells or tissues in the body to target their pharmacological effects and improve their therapeutic index and safety.