Related Experiment Video
Updated: May 5, 2026
Scalable Biomanufacturing Workflow to Produce and Isolate Natural Killer Cell-Derived Extracellular Vesicle-Based Cancer Biotherapeutics
Published on: August 16, 2024
Distinct Biodistribution of Natural Killer Cell-Derived Exosomes in an Orthotopic A549 Lung Cancer Mouse Model:
Yen-Lien Chou1, Kuo-Feng Hsu2, Ssu-Han Chen3
1Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei 114202, Taiwan.
Abstract:
Background: Exosomes (Exos) derived from immune cells are emerging as potent drug delivery vectors. However, their biodistribution in clinically relevant lung cancer models remains underexplored. This study aimed to evaluate the lung-homing ability of NK cell Exos (NK-Exos) compared to mesenchymal stem cell Exos (MSC-Exos) in an orthotopic lung cancer model. Methods: Male SCID mice were orthotopically injected with luciferase-tagged A549 cells into the left lung to establish the tumor model. Mice were randomized into four groups: G1 (Healthy Control), G2 (Tumor Control + PBS), G3 (Tumor + DiR-labeled NK-Exos; 5 µM DiR + 5-7 × 109 Exo particles/100 μL/mouse), and G4 (Tumor + DiR-labeled MSC-Exos; 5 µM DiR + 5-7 × 109 Exo particles/100 μL/mouse). Six hours (15 min, 1 h, 2 h, 4 h, 6 h) post-intravenous injection, ex vivo biodistribution was assessed using the MILabs Spectrum imaging system. Results: Umbilical cord blood-NK-Exos (UCB-NK-Exos; G3) exhibited superior accumulation in lung tissues compared to UCB-MSC-Exos (G4), suggesting enhanced pulmonary retention. Intra-pulmonary analysis revealed an asymmetric distribution, with significantly higher radiant efficiency in the right lung (non-tumor bearing) compared to the left lung (tumor injection site) across Exo-treated groups. Conclusions: UCB-NK-Exos demonstrate distinct lung-targeting properties superior to MSC-Exos, supporting their potential as therapeutic carriers.
