Lung cancer remains a leading cause of cancer mortality, with most patients presenting at advanced stages when curative options are limited. Chemotherapy continues to be a central oncologic modality, yet dose‑limiting systemic toxicities restrict therapeutic intensity. Many anticancer agents exhibit significant hydrophobicity and poor solubility, necessitating incorporation into engineered biological or synthetic nanocarriers to enhance solubilization, improve pharmacokinetics, expand the therapeutic window, and reduce off‑target toxicity.
In recent years, extracellular vesicles (EVs) have emerged as highly promising drug carriers. Secreted by all cell types, EVs are small, circulatory, non‑immunogenic, and capable of traversing cellular membranes while evading lysosomal degradation, enabling efficient cytosolic delivery of diverse cargos. These unique attributes have accelerated the exploration of EVs as delivery systems across numerous diseases, including cancer.
Over the past 15 years, Dr. Ramesh’s laboratory at the University of Oklahoma in Oklahoma City, USA, has extensively investigated EVs for therapeutic and diagnostic applications. The group recently developed an EV‑based drug delivery platform for lung cancer treatment by integrating nanotechnology, ligand‑mediated targeting, and controlled drug release chemistry into a single system. Surface modification with transferrin (Tf) further enhanced tumor‑specific uptake through transferrin receptor (TfR) overexpression in lung cancer cells.
The engineered tumor‑targeted multifunctional extracellular vesicles (tt‑Mfn‑EVs) encapsulate gold nanoparticle-cisplatin conjugates and incorporate transferrin ligands to achieve pH‑responsive, TfR‑mediated tumor uptake and selective cytotoxicity. These tt‑Mfn‑EVs demonstrated accelerated drug release under acidic conditions, enhanced cellular uptake and intracellular drug delivery, increased apoptosis and DNA damage in TfR‑high lung cancer cells, and minimal toxicity toward normal human lung and kidney cells, highlighting their potential to reduce off‑target toxicity and cisplatin‑induced nephrotoxicity.
Through this multifunctional design, EVs in this study function not as passive carriers but as actively, tumor‑targeted, tumor environment‑responsive delivery systems capable of improving chemotherapeutic precision, minimizing systemic toxicity, and supporting future theranostic applications.
The platform also leverages the photothermal properties of GNP‑loaded EVs to enable integrated photothermal-chemotherapeutic intervention. This approach establishes a versatile EV‑nanotechnology system that enhances targeted delivery, enables controlled drug release, and supports combinatorial therapeutic modalities for next‑generation cancer treatment. The work entitled “Tumor‑targeted multifunctional extracellular vesicles as drug carriers for lung cancer therapy”, was published in Extracellular Vesicles and Circulating Nucleic Acids (published on Dec. 23, 2025).
DOI: 10.20517/evcna.2025.39