Inhibition of orthotopic secondary hepatic carcinoma in mice by doxorubicin-loaded electrospun polylactide nanofibers
Inhibition of orthotopic secondary hepatic carcinoma in mice by doxorubicin-loaded electrospun polylactide nanofibers
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负载阿霉素的电纺聚丙交酯纳米纤维对小鼠原位继发性肝癌的抑制作用
DOI：
10.1039/c2tb00121g
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发表时间：
2013-01-01
影响因子：
7
通讯作者：
Jing, Xiabin
中科院分区：
文献类型：
--
作者：
Liu, Shi;Zhou, Guangyuan;Jing, Xiabin
对于无法切除的肝癌的治疗或预防术后肿瘤复发，局部化疗可能是一个不错的选择。进行了一项初步研究，以检查负载阿霉素的聚丙交酯电纺纳米纤维（Dox 纤维）作为局部化疗系统对抗继发性肝癌（SHCC）的功效。通过将小鼠乳腺癌EMT6细胞注射到Balb/c小鼠的左肝叶和门静脉中，分别制备结节性和弥漫性SHCC（NSHCC和DSHCC），制备两个原位SHCC模型。通过覆盖NSHCC肿瘤表面，并在剖腹探查后用Dox纤维垫包裹整个肝脏DSHCC，NSHCC的生长明显受到抑制，DSHCC小鼠的中位生存时间从14天增加到38天。安全性研究表明，空白聚丙交酯纤维（PLLA 纤维）和 Dox 纤维都会在健康小鼠的肝组织中引发典型的炎症反应。 Dox 纤维引起肝实质纤维垫覆盖区域的急性、可逆性损伤。但在42天的实验期间，未观察到邻近肝组织损伤和全身不良反应。为了解释 Dox 纤维治疗的功效和安全性，对纤维垫中 Dox 的体内释放和生物分布进行了研究。 Dox 在前 24 小时内迅速从纤维垫中释放，最好位于肝组织纤维垫覆盖的区域。总之，负载 Dox 的聚丙交酯纤维可用于肝癌的局部化疗。
For the treatment of unresectable liver cancer or for the prevention of post-surgery tumor recurrence, local chemotherapy is probably a good choice. A pilot study was carried out to examine the efficacy of doxorubicin-loaded polylactide electrospun nanofibers (Dox fibers) as a local chemotherapy system against secondary hepatic carcinoma (SHCC). Two orthotopic SHCC models were prepared by injecting murine mammary carcinoma EMT6 cells into the left hepatic lobe and into the portal vein of Balb/c mice, resulting in nodular and diffuse SHCC (NSHCC and DSHCC), respectively. By covering the surface of the NSHCC tumor and by wrapping the whole liver bearing DSHCC with the Dox fiber-mat after explorative laparotomy, the growth of NSHCC was significantly inhibited and median survival time of the mice bearing DSHCC was increased from 14 days to 38 days. Safety study suggested that both blank polylactide fibers (PLLA fibers) and Dox fibers ignited typical inflammatory response in the liver tissue of healthy mice. Acute, reversible impairment on fiber-mat-covered area of hepatic parenchyma was induced by Dox fibers. But neither injury to neighboring liver tissue nor systemic adverse reactions were observed during the experimental period of 42 days. In order to explain the efficacy and safety of Dox fiber treatment, in vivo release and biodistribution of Dox from the fiber-mat was investigated. Dox was rapidly released from the fiber-mat in the first 24 h, preferably localized in fiber-mat-covered area of liver tissue. In conclusion, Dox-loaded polylactide fibers might be used for local chemotherapy of liver cancers.