叶酸壳聚糖吉西他滨靶向胰腺癌核壳纳米粒。
Folate-chitosan-gemcitabine core-shell nanoparticles targeted to pancreatic cancer.
机构信息
Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210029, China;
出版信息
Chin J Cancer Res. 2013 Oct;25(5):527-35. doi: 10.3978/j.issn.1000-9604.2013.09.04.
OBJECTIVE
Human pancreatic cancer is one of the most common clinical malignancies. The effect of comprehensive treatment based on surgery is general. The effects of chemotherapy were not obvious mainly because of lack of targeting and chemoresistance in pancreatic cancer. This study aimed to investigate the effects of folate receptor (FR)-mediated gemcitabine FA-Chi-Gem nanoparticles with a core-shell structure by electrostatic spray on pancreatic cancer.
METHODS
In this study, the levels of expression of FR in six human pancreatic cancer cell lines were studied by immunohistochemical analysis. The uptake rate of isothiocyanate-labeled FA-Chi nanoparticles in FR high expression cell line COLO357 was assessed by fluorescence microscope and the inhibition rate of FA-Chi-Gem nanoparticles on COLO357 cells was evaluated by MTT assay. Moreover, the biodistribution of PEG-FA-ICGDER02-Chi in the orthotopic pancreatic tumor model was observed using near-infrared imaging and the human pancreatic cancer orthotopic xenografts were treated with different nanoparticles and normal saline control.
RESULTS
The expression of FR in COLO357 was the highest among the six pancreatic cancer cell lines. The FR mainly distributed on cell membrane and fewer in the cytoplasm in pancreatic cancer. Moreover, the absorption rate of the FA-Chi-Gem nanoparticles was more than the Chi nanoparticles without FA modified. The proliferation of COLO357 was significantly inhibited by FA-Chi-Gem nanoparticles. The PEG-FA-ICGDER02-Chi nanoparticles were enriched in tumor tissue in human pancreatic cancer xenografts, while non-targeted nanoparticles were mainly in normal liver tissue. PEG-FA-Gem-Chi significantly inhibited the growth of human pancreatic cancer xenografts (PEG-FA-Gem-Chi vs. Gem, t=22.950, P=0.000).
CONCLUSIONS
PEG-FA-FITC-Chi nanoparticles might be an effective targeted drug for treating human FR-positive pancreatic cancer.
目的
人胰腺癌是最常见的临床恶性肿瘤之一。基于手术的综合治疗效果一般。胰腺癌化疗效果不明显主要是因为缺乏靶向性和化疗耐药性。本研究旨在探讨静电喷雾法制备的叶酸受体（FR）介导的载吉西他滨的核壳结构 FA-Chi-Gem 纳米粒对胰腺癌的作用。
方法
本研究通过免疫组化分析研究了 6 个人胰腺癌细胞系中 FR 的表达水平。通过荧光显微镜评估 FR 高表达细胞系 COLO357 对异硫氰酸标记的 FA-Chi 纳米粒的摄取率，并通过 MTT 测定评估 FA-Chi-Gem 纳米粒对 COLO357 细胞的抑制率。此外，通过近红外成像观察 PEG-FA-ICGDER02-Chi 在原位胰腺肿瘤模型中的生物分布，并使用不同的纳米粒和生理盐水对照处理人胰腺癌原位异种移植。
结果
在 6 个人胰腺癌细胞系中，COLO357 中 FR 的表达最高。FR 主要分布在细胞膜上，细胞质中较少。此外，FA 修饰的 Chi-Gem 纳米粒的吸收率高于未修饰 FA 的 Chi 纳米粒。FA-Chi-Gem 纳米粒显著抑制了 COLO357 的增殖。PEG-FA-ICGDER02-Chi 纳米粒在人胰腺癌异种移植瘤组织中富集，而非靶向纳米粒主要在正常肝组织中。PEG-FA-Gem-Chi 显著抑制了人胰腺癌异种移植瘤的生长（PEG-FA-Gem-Chi 与 Gem 相比，t=22.950，P=0.000）。
结论
PEG-FA-FITC-Chi 纳米粒可能是治疗人 FR 阳性胰腺癌的有效靶向药物。
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