Time-programmed DCA and oxaliplatin release by multilayered nanofiber mats in prevention of local cancer recurrence following surgery.
Time-programmed DCA and oxaliplatin release by multilayered nanofiber mats in prevention of local cancer recurrence following surgery.
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DOI：
10.1016/j.jconrel.2016.05.046
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发表时间：
2016-08
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影响因子：
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通讯作者：
Zhi-yun Zhang;Shi Liu;Yanxin Qi;Dongfang Zhou;Zhigang Xie;X. Jing;Xuesi Chen;Yubin Huang
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文献类型：
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作者：
Zhi-yun Zhang;Shi Liu;Yanxin Qi;Dongfang Zhou;Zhigang Xie;X. Jing;Xuesi Chen;Yubin Huang
癌症治疗手术后的局部复发仍然是一个重大的临床挑战。为了提高抗肿瘤活性，同时将毒性保持在可接受的水平，以预防局部癌症复发，我们展示了一种双载药多层纤维垫策略，其中将 DCA 和奥沙利铂共静电纺成所得织物的不同层，并将载奥沙利铂纤维层密封在基底膜层和其他两个纤维层之间。双载药多层纤维垫表现出定时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地促进癌细胞凋亡，随后低浓度的奥沙利铂杀死剩余的癌细胞。将双载药多层纤维垫植入小鼠模型的宫颈癌切除边缘后，与载药单层纤维垫相比，在 30 天内显示出增强的抗复发功效和降低的副作用。 DCA 和奥沙利铂在多层纳米纤维垫内的时间编程组合似乎是切除后局部癌症治疗的一种有前途的策略。
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 30 days 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.