State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
J Control Release. 2016 Aug 10;235:125-133. doi: 10.1016/j.jconrel.2016.05.046. Epub 2016 May 21.
Local recurrence following surgery in cancer treatment remains a major clinical challenge. To increase antitumor activity but maintain toxicity in an acceptable level in prevention of local cancer recurrence, we demonstrated a dual drug-loaded multilayered fiber mats strategy, in which DCA and oxaliplatin were co-electrospun into the distinct layer of resultant fabrics and the oxaliplatin-loaded fibers layer was sealed between the basement film layer and other two fibers layers. The dual drug-loaded multilayered fiber mats exhibit time-programmed dual release behavior and synergistic effect upon cancer cells. Nontoxic DCA selectively promotes apoptosis of cancer cells through modulating cellular metabolism, and oxaliplatin subsequently kills the remained cancer cells in a low concentration. After implantation on the resection margin of cervical carcinoma on a murine model, the dual drug-loaded multilayered fiber mats displayed enhanced anti-recurrence efficacy and decreased side toxic effects over 30days compared with drug-loaded monolayered fiber mats. The time-programmed combination of DCA and oxaliplatin within multilayered nanofiber mats appears to be a promising strategy for local cancer treatment following resection.
手术后癌症治疗中的局部复发仍然是一个主要的临床挑战。为了在预防局部癌症复发的同时提高抗肿瘤活性并将毒性保持在可接受的水平，我们展示了一种双重药物负载的多层纤维垫策略，其中 DCA 和奥沙利铂共静电纺丝到不同的纤维层中，并且载奥沙利铂的纤维层被密封在基底膜层和其他两层纤维层之间。双重药物负载的多层纤维垫表现出时间控制的双重释放行为和对癌细胞的协同作用。无毒的 DCA 通过调节细胞代谢选择性促进癌细胞凋亡，而低浓度的奥沙利铂随后杀死残留的癌细胞。在小鼠模型的宫颈癌切除边缘植入后，与载药单层纤维垫相比，双重药物负载的多层纤维垫在 30 天内显示出增强的抗复发效果和降低的副作用。多层纳米纤维垫内 DCA 和奥沙利铂的时间控制组合似乎是一种有前途的局部癌症治疗策略，适用于手术后的治疗。
