Abstract
Targeted drug delivery significantly enhances therapeutic efficacy across various diseases, particularly in cancer treatments, where conventional approaches such as chemotherapy and radiotherapy often cause severe side effects. In this context, nucleic acid aptamers-short, single-stranded DNA or RNA oligonucleotides capable of binding specific targets with high affinity-have emerged as promising tools for precision drug delivery and therapy. Aptamers can be selected against whole, living cells using SELEX and chemically modified for diverse applications. Their chemical versatility and specific binding capabilities allow aptamers to be engineered into aptamer-drug conjugates, nanoparticles, DNA origami structures, and bi-/multivalent or bispecific constructs. These platforms enable selective recognition of unique molecular signatures on cells or small molecules, facilitating highly targeted drug delivery and controlled release at the disease site. Such precision reduces systemic toxicity and enhances therapeutic outcomes. Compared to antibodies, aptamers offer several advantages, including faster tissue penetration, lower immunogenicity, greater chemical stability, and improved bioavailability in vivo. This review highlights recent advances in aptamer modification strategies-both covalent and non-covalent-for conjugation with chemotherapeutic agents, gold nanoparticles (GNPs), and photosensitizers. We further assess their potential as drug delivery vehicles and therapeutic agents and discuss how these innovations are driving progress in precision medicine.