Nanofibrous poly(L-lactide-co-D,L-lactide) (coPLA) or coPLA/poly(ethylene glycol) implants loaded with plant polyphenolic compound gossypol (GOS) with anti-tumor activity were fabricated by electrospinning. Implants containing quaternized chitosan (QCh) were prepared by coating of the obtained fibrous materials with a thin film of cross-linked QCh. The morphology of the implants and chemical composition of the implant surface were studied by means of scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). In vitro cytotoxicity assay showed that GOS-loaded nanofibrous implants, both non-coated and QCh-coated displayed about two-fold higher inhibitory activity against Graffi tumor cells than that of free GOS at the 72nd h of incubation. As evidenced by the performed fluorescence microscopy analyses and SEM observations, the anti-tumor activity of the fibrous implants was mainly due to induction of apoptosis. The experiments in which the implants containing both QCh and GOS were placed locally into the tumor site after the tumor extirpation showed an increase in the survival rate and a lower rate of recurrence in the operative field and of metastases in regional lymph nodes. In this case, 40% of hamsters were alive on the 45th day of implantation and they did not show any clinical sign of recurrence in the operative field and metastases in the regional lymph nodes.

译文

:通过电纺丝制备了负载有抗肿瘤活性的植物多酚化合物棉酚(GOS)的纳米纤维聚(L-丙交酯-co-D,L-丙交酯)(coPLA)或coPLA /聚乙二醇。含有季铵化壳聚糖(QCh)的植入物是通过在获得的纤维材料上涂覆一层交联的QCh薄膜来制备的。通过扫描电子显微镜(SEM)和X射线光电子能谱(XPS)研究了植入物的形态和植入物表面的化学成分。体外细胞毒性试验表明,在孵育的第72小时,未涂覆和QCh涂覆的GOS负载的纳米纤维植入物对Graffi肿瘤细胞的抑制活性比游离GOS约高两倍。如通过进行的荧光显微镜分析和SEM观察所证明的,纤维植入物的抗肿瘤活性主要归因于细胞凋亡的诱导。肿瘤切除后,将同时含有QCh和GOS的植入物局部放置到肿瘤部位的实验表明,其生存率提高了,手术区域的复发率降低了,局部淋巴结转移率也降低了。在这种情况下,有40%的仓鼠在植入后第45天还活着,并且在手术区域未见任何复发的临床迹象,在局部淋巴结也未见转移。

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