RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy
RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy
复制标题
RGD 结合的白蛋白纳米颗粒作为胰腺癌治疗的新型递送载体
DOI：
10.4161/cbt.13.4.18692
复制
发表时间：
2012-02-15
影响因子：
3.6
通讯作者：
Yu, Xianjun
中科院分区：
文献类型：
--
作者：
Ji, Shunrong;Xu, Jin;Yu, Xianjun
整合素α v β 3受体在包括胰腺癌细胞在内的几种类型的癌细胞上表达，在肿瘤生长和转移中起重要作用。靶向癌细胞上的整合素α v β 3受体的能力增加了靶向治疗的功效并减少了副作用。本研究的目的是开发一种新型的精氨酸-甘氨酸-天冬氨酸（RGD）肽偶联白蛋白纳米粒，以增强胰腺癌细胞通过受体介导的内吞作用对抗癌药物的细胞内摄取。在细胞摄取研究中，通过荧光分光光度计测定，在BxPC 3细胞中的RGD缀合的BSANP的荧光信号高于没有RGD缀合的BSANP。我们还发现BSANP以时间和浓度依赖性的方式与BxPC 3细胞结合。过量的游离RGD肽抑制胰腺癌细胞对RGD缀合的BSANP的摄取，表明结合和/或摄取由α v β 3受体介导。此外，通过使用激光扫描共聚焦显微镜，发现纳米颗粒位于靠近细胞核。MTT法检测无明显细胞毒性。通过使用RGD肽将负载吉西他滨的纳米颗粒靶向BxPC-3细胞来改善体外和体内抗肿瘤功效。因此，RGD-缀合的BSANP作为一种有效的药物递送系统具有很大的潜力，以将治疗剂递送到胰腺癌。
Integrin alpha v beta 3 receptor is expressed on several types of cancer cells, including pancreatic cancer cells, and plays an important role in tumor growth and metastasis. The ability to target the integrin alpha v beta 3 receptor on cancer cells increases the efficacy of targeted therapy and reduces the side effects. The aim of this study is to develop a novel arginine-glycine-aspartic acid (RGD) peptide-conjugated albumin nanoparticle to enhance the intracellular uptake of anticancer drug into the pancreatic cancer cells through receptor-mediated endocytosis. In cellular uptake studies, the fluorescent signal of RGD-conjugated BSANPs in BxPC3 cells was higher than that of BSANPs without RGD conjugation as determined by fluorescence spectrophotometer. We also found that BSANPs bound to BxPC3 cells in a time-and concentration-dependent manner. The uptake of RGD-conjugated BSANPs by pancreatic cancer cells was inhibited by an excess amount of free RGD peptide, indicating that the binding and/or uptake were mediated by the alpha v beta 3 receptor. Furthermore, the nanoparticles were found to be located close to the nuclei by using laser scanning confocal microscopy. Besides, no significant in vitro cytotoxicity was observed as measured with MTT assay. Both in vitro and in vivo antitumor efficacy was improved by targeting gemcitabine-loaded nanoparticles to BxPC-3 cells using RGD peptides. Therefore, the RGD-conjugated BSANPs hold great potential as an effective drug delivery system to deliver therapeutic agents to pancreatic cancer.