Aptamer-Functionalized Exosomes: Elucidating the Cellular Uptake Mechanism and the Potential for Cancer-Targeted Chemotherapy

TLDR

Exosomes are nanoscale natural vehicles that transport biomolecules for cell‑to‑cell communication and hold promise for therapeutic delivery, yet enhancing their capacity through functionalization with targeting ligands and understanding their uptake mechanisms remains a challenge. This study aims to develop an aptamer‑functionalized exosome platform using diacyllipid–aptamer conjugates for cell‑type‑specific delivery of therapeutics and to elucidate its cellular uptake mechanism. The authors functionalized exosomes with diacyllipid–aptamer conjugates to create Apt‑Exos, a nanoplatform designed for targeted delivery of molecular therapeutics. Apt‑Exos exhibited distinct uptake behavior compared to free exosomes and efficiently delivered drugs or fluorophores to cancer cells, demonstrating a promising platform for cancer theranostics.

Abstract

Exosomes (Exos) are nanoscale natural vehicles for transporting biomolecules to facilitate cell-to-cell communication, indicating a high potential of them for delivering therapeutics/diagnostics. To improve their delivery capacity, a simple, noninvasive, and efficient strategy for functionalizing Exos with effective targeting ligands as well as elucidation of the cellular uptake mechanism of these functionalized Exos was found be to necessary, but remained a challenge. In this work, we used diacyllipid–aptamer conjugates as the targeting ligand to develop an aptamer-functionalized Exos (Apt-Exos) nanoplatform for cell type-specific delivery of molecular therapeutics. The cellular uptake mechanism of Apt-Exos was investigated in details, and distinct behavior was observed in comparison to free Exos. By combining the excellent molecular recognition capability of aptamers and the superiority of Exos as natural vehicles, Apt-Exos can efficiently deliver molecular drugs/fluorophores to target cancer cells, providing a promising delivery platform for cancer theranostics.