Xiao Jun, Yu Haibo
Department of Surgery, Wenzhou Central Hospital, Wenzhou, Zhejiang, China (mainland).
Med Sci Monit. 2017 Apr 3;23:1613-1620. doi: 10.12659/msm.901292.
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.
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。
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。
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。
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。