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吉西他滨共轭壳聚糖与双抗体(Abc-GC-吉西他滨纳米颗粒)增强吉西他滨的细胞质摄取并抑制人SW1990胰腺癌细胞的增殖和转移。

Gemcitabine Conjugated Chitosan and Double Antibodies (Abc-GC-Gemcitabine Nanoparticles) Enhanced Cytoplasmic Uptake of Gemcitabine and Inhibit Proliferation and Metastasis In Human SW1990 Pancreatic Cancer Cells.

作者信息

Xiao Jun, Yu Haibo

机构信息

Department of Surgery, Wenzhou Central Hospital, Wenzhou, Zhejiang, China (mainland).

出版信息

Med Sci Monit. 2017 Apr 3;23:1613-1620. doi: 10.12659/msm.901292.

DOI:10.12659/msm.901292
PMID:28366930
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5388304/
Abstract

BACKGROUND Pancreatic cancer is considered a chemoresistant neoplasm with extremely dismal prognosis and gemcitabine treatment is associated with many side effects and poor overall survival. The study aimed at developing a new nanobioconjugate, which specifically delivered gemcitabine and anti-EGFR antibody into pancreatic cancer cells. MATERIAL AND METHODS The novel nanodrug is based on chitosan platform, which is non-toxic, biocompatibility and biodegradable. We measured the effects of proliferation and metastasis on SW1990 by CCK-8 assay, colony formation assay, wound healing assay and Transwell assay. The expression of related proteins were evaluated by Western blot. RESULTS We synthesized Abc-GC-gemcitabine nanoparticles successfully with the encapsulation rate of nanobioconjugates was 91.63% and the drug loadings was 9.97%. Both GC-gemcitabine microspheres solution (GC group) and Abc-GC-gemcitabine microspheres solution (Abc group) inhibited cells proliferation, colony formation, migration and invasion in SW1990 cells dramatically. Moreover, Abc-GC-gemcitabine microspheres expressed more significant inhibited action than GC-gemcitabine microspheres efficiently CONCLUSIONS Our data suggested that Abc-GC-gemcitabine nanoparticles could have promising potential in treating metastasized and chemoresistant pancreatic cancer by enhancing the drug efficacy and minimizing off target effects.

摘要

背景

胰腺癌被认为是一种具有极低预后的化疗耐药性肿瘤,吉西他滨治疗伴随着许多副作用且总体生存率较低。本研究旨在开发一种新型纳米生物共轭物,其能够将吉西他滨和抗表皮生长因子受体(EGFR)抗体特异性递送至胰腺癌细胞中。

材料与方法

这种新型纳米药物基于壳聚糖平台,壳聚糖无毒、具有生物相容性且可生物降解。我们通过CCK-8法、集落形成试验、伤口愈合试验和Transwell试验来检测其对SW1990细胞增殖和转移的影响。通过蛋白质印迹法评估相关蛋白的表达。

结果

我们成功合成了Abc-GC-吉西他滨纳米颗粒,纳米生物共轭物的包封率为91.63%,载药量为9.97%。GC-吉西他滨微球溶液(GC组)和Abc-GC-吉西他滨微球溶液(Abc组)均显著抑制SW1990细胞的增殖、集落形成、迁移和侵袭。此外,Abc-GC-吉西他滨微球比GC-吉西他滨微球表现出更显著的抑制作用。

结论

我们的数据表明,Abc-GC-吉西他滨纳米颗粒通过增强药物疗效并最大限度地减少脱靶效应,在治疗转移性和化疗耐药性胰腺癌方面可能具有广阔的前景。

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