Prevention of lung cancer recurrence using cisplatin-loaded superhydrophobic nanofiber meshes.
Prevention of lung cancer recurrence using cisplatin-loaded superhydrophobic nanofiber meshes.
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DOI：
10.1016/j.biomaterials.2015.10.060
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发表时间：
2016-01
期刊：
影响因子：
14
通讯作者：
Grinstaff MW
中科院分区：
文献类型：
--
作者：
Kaplan JA;Liu R;Freedman JD;Padera R;Schwartz J;Colson YL;Grinstaff MW
对于早期肺癌患者来说，手术切除后的局部肿瘤复发是一个值得关注的问题，它源于术后遗留的显微病变。在这里，我们应用局部给药策略来对抗肺癌切除术后局部复发，使用无纺布、可生物降解的纳米纤维网负载顺铂。这种网是用一种可扩展的静电纺丝工艺由两种生物相容性聚合物——聚己内酯和聚甘油单硬脂酸-共己内酯——制成的，为动态组织（如肺）提供了良好的机械性能。由于其粗糙的纳米结构和疏水聚合物组成，这些网状物表现出超疏水性，正是这种不润湿的性质维持了顺铂在90天内的线性释放，并在体外Lewis肺癌（LLC）细胞试验中证明了抗癌功效。体内评估显示，与同等剂量的标准腹腔内顺铂治疗相比，负载顺铂的超疏水网预防LLC手术切除小鼠模型局部癌症复发的中位无复发生存期（p = 0.0006）显著增加（p = 0.0006）至bb0.23天。这些结果强调了补充细胞减少手术和局部给药策略对改善肺癌肿瘤切除术患者预后的重要性。
For early stage lung cancer patients, local cancer recurrence after surgical resection is a significant concern and stems from microscopic disease left behind after surgery. Here we apply a local drug delivery strategy to combat local lung cancer recurrence after resection using non-woven, biodegradable nanofiber meshes loaded with cisplatin. The meshes are fabricated using a scalable electrospinning process from two biocompatible polymers—polycaprolactone and poly(glycerol monostearate-co-caprolactone)—to afford favorable mechanical properties for use in a dynamic tissue such as the lung. Owing to their rough nanostructure and hydrophobic polymer composition, these meshes exhibit superhydrophobicity, and it is this non-wetting nature that sustains the release of cisplatin in a linear fashion over ~90 days, with anti-cancer efficacy demonstrated using an in vitro Lewis Lung carcinoma (LLC) cell assay. The in vivo evaluation of cisplatin-loaded superhydrophobic meshes in the prevention of local cancer recurrence in a murine model of LLC surgical resection demonstrated a statistically significant increase (p = 0.0006) in median recurrence-free survival to >23 days, compared to standard intraperitoneal cisplatin therapy of equivalent dose. These results emphasize the importance of supplementing cytoreductive surgery with local drug delivery strategies to improve prognosis for lung cancer patients undergoing tumor resection.