EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model.
EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model.
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DOI：
10.1016/j.nano.2015.11.010
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Amiji M
中科院分区：
文献类型：
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作者：
Singh A;Xu J;Mattheolabakis G;Amiji M
在这项研究中，我们制定了氧化还原反应性表皮生长因子受体（EGFR）靶向B型明胶纳米颗粒作为靶向载体的全身吉西他滨治疗胰腺癌。通过乙醇诱导的去溶剂化过程形成明胶纳米粒以包封结合的药物。纳米颗粒的表面用聚（乙二醇）（PEG）链修饰以赋予增强的循环时间，并用EGFR靶向肽修饰以赋予靶特异性。我们在Panc-1人胰腺导管腺癌细胞中的体外研究证实，通过二硫键裂解释放的EGFR靶向明胶纳米颗粒包封的吉西他滨具有显著改善的细胞毒性特征。此外，在携带原位胰腺癌肿瘤的SCID米色小鼠中评价了体内抗癌活性，这证实了EGFR靶向明胶纳米颗粒可以有效地将吉西他滨递送至肿瘤，从而导致与溶液中的药物相比更高的治疗益处。
In this study, we have formulated redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a targeted vector for systemic delivery of gemcitabine therapy in pancreatic cancer. The gelatin nanoparticles were formed by ethanol-induced desolvation process to encapsulate the bound drug. The surface of the nanoparticles was decorated either with poly(ethylene glycol) (PEG) chains to impart enhanced circulation time and with EGFR targeting peptide to confer target specificity. Our in vitro studies in Panc-1 human pancreatic ductal adenocarcinoma cells confirm that gemcitabine encapsulated in EGFR-targeted gelatin nanoparticles, released through disulfide bond cleavage, had a significantly improved cytotoxic profile. Further, the in vivo anticancer activity was evaluated in an orthotopic pancreatic adenocarcinoma tumor bearing SCID beige mice, which confirmed that EGFR-targeted gelatin nanoparticles could efficiently deliver gemcitabine to the tumor leading to higher therapeutic benefit as compared to the drug in solution.