肿瘤细胞治疗研究
英文原题：Distinct Biodistribution of Natural Killer Cell-Derived Exosomes in an Orthotopic A549 Lung Cancer Mouse Model: Implications for Potent Targeted Drug Delivery.
Distinct Biodistribution of Natural Killer Cell-Derived Exosomes in an Orthotopic A549 Lung Cancer Mouse Model: Implications for Potent Targeted Drug Delivery.
背景：源自免疫细胞的外泌体（Exos）正成为有效的药物递送载体。
背景：源自免疫细胞的外泌体（Exos）正成为有效的药物递送载体。然而，其在临床相关肺癌模型中的生物分布仍未得到充分探索。本研究旨在评估NK细胞外泌体（NK-Exos）与间充质干细胞外泌体（MSC-Exos）在原位肺癌模型中的肺归巢能力。 方法：将携带荧光素酶标签的A549细胞原位注射至雄性SCID小鼠左肺以建立肿瘤模型。小鼠随机分为四组：G1（健康对照）、G2（肿瘤对照 + PBS）、G3（肿瘤 + DiR标记的NK-Exos；5 µM DiR + 5-7 × 10 9 Exo颗粒/100 μL/小鼠）和G4（肿瘤 + DiR标记的MSC-Exos；5 µM DiR + 5-7 × 10 9 Exo颗粒/100 μL/小鼠）。静脉注射后六小时（15 min、1 h、2 h、4 h、6 h），使用MILabs Spectrum成像系统评估离体生物分布。 结果：与UCB-MSC-Exos（G4）相比，脐带血NK-Exos（UCB-NK-Exos；G3）在肺组织中表现出更优的蓄积，提示其肺滞留增强。肺内分析显示不对称分布，在Exo处理组中，右肺（非荷瘤）的辐射效率显著高于左肺（肿瘤注射部位）。 结论：UCB-NK-Exos表现出优于MSC-Exos的独特肺靶向特性，支持其作为治疗载体的潜力。
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 × 10 9 Exo particles/100 μL/mouse), and G4 (Tumor + DiR-labeled MSC-Exos; 5 µM DiR + 5-7 × 10 9 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.
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