Aptamer-functionalized nanoparticles for cancer targeting: conjugation strategies, current applications and future...

Aptamers have emerged as highly versatile targeting ligands for nanomedicine due to their small size, low immunogenicity, and programmable chemical modification. Their integration into nanoparticle-based systems has enabled precise molecular recognition while preserving the physicochemical properties of diverse nanocarriers. Recent studies have demonstrated that aptamer functionalization can increase cellular uptake and tumor accumulation by several-fold compared to non-targeted systems, resulting in significantly enhanced therapeutic efficacy in both synthetic nanoparticle and extracellular vesicle (EV)-based platforms. This Special Report provides a critical overview of current strategies for aptamer functionalization, with emphasis on conjugation chemistries, nano-bio interface engineering, and translational considerations. We also highlight emerging approaches, including bispecific targeting and programmable nucleic-acid nanostructures, which further improve targeting precision and functional control. Overall, this work outlines key design principles and future directions for the development of next-generation aptamer-guided nanomedicines.