Kaplan Jonah A, Liu Rong, Freedman Jonathan D, Padera Robert, Schwartz John, Colson Yolonda L, Grinstaff Mark W
Department of Biomedical Engineering, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; Department of Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA; Department of Medicine, Boston University, 590 Commonwealth Ave., Boston, MA 02215, USA.
Department of Surgery, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, USA.
Biomaterials. 2016 Jan;76:273-81. doi: 10.1016/j.biomaterials.2015.10.060. Epub 2015 Oct 27.
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.
对于早期肺癌患者而言，手术切除后局部癌症复发是一个重大问题，其源于手术后残留的微小病灶。在此，我们应用一种局部给药策略，使用负载顺铂的非织造、可生物降解纳米纤维网来对抗切除术后的局部肺癌复发。这些网是通过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（甘油单硬脂酸酯 - 共 - 己内酯）制成，以提供适用于如肺这样的动态组织的良好机械性能。由于其粗糙的纳米结构和疏水性聚合物组成，这些网表现出超疏水性，正是这种不湿润的性质使顺铂在约90天内以线性方式持续释放，体外Lewis肺癌（LLC）细胞试验证明了其抗癌功效。在LLC手术切除小鼠模型中，对负载顺铂的超疏水网预防局部癌症复发的体内评估表明，与等效剂量的标准腹腔内顺铂治疗相比，无复发生存期的中位数在统计学上显著增加（p = 0.0006）至>23天。这些结果强调了用局部给药策略补充减瘤手术以改善接受肿瘤切除的肺癌患者预后的重要性。
