Targeting Pancreatic Cancer Cells with Peptide-Functionalized Polymeric Magnetic Nanoparticles

Targeting Pancreatic Cancer Cells with Peptide-Functionalized Polymeric Magnetic Nanoparticles
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用肽功能化的聚合物磁性纳米颗粒靶向胰腺癌细胞

DOI:
10.3390/ijms20122988
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发表时间:
2019-06
影响因子:
5.6
通讯作者:
Zuhua Wang
Zuhua Wang
中科院分区:
生物学2区
文献类型:
--
作者:
Xiuliang Zhu;Nan Lu;Ying Zhou;Shaoyan Xuan;Jiaojiao Zhang;Francesca Giampieri;Yongping Zhang;Fangfang Yang;Risheng Yu;Maurizio Battino;Zuhua Wang

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胰腺癌是一种隐匿性、高度恶性的肿瘤,其早期诊断在肿瘤治疗过程中起着越来越重要的作用。在这项研究中,我们开发了一种用于MRI造影剂的聚合物磁共振成像(MRI)纳米平台。为了改善MRI造影剂的肿瘤靶向递送,我们采用胰腺癌靶向CKAAKN肽来制备肽官能化的两亲性透明质酸-维生素E琥珀酸酯聚合物(CKAAKN-HA-VES),用于递送超小超顺磁性氧化铁(USPIO),即CKAAKN-HA-VES@USPIO。通过对CKAAKN肽的修饰,CKAAKN-HA-VES@USPIO可以特异性地内化到CKAAKN阳性的BxPC-3细胞中。与正常胰腺细胞相比,CKAAKN-HA-VES@USPIO纳米颗粒在胰腺癌细胞中表现出更特异性的蓄积,并且与CKAAKN阴性HPDE 6-C7细胞和非靶向HA-VES@USPIO纳米颗粒相比,在CKAAKN阳性BxPC-3细胞中观察到明显的信号强度降低。结果表明,我们的聚合物MRI纳米平台可以通过CKAAKN肽与胰腺癌细胞膜受体的特异性结合选择性地内化到CKAAKN阳性胰腺癌细胞中,这为胰腺癌诊断提供了一种新型的高特异性聚合物MRI造影剂,使其成为磁共振成像对比增强的非常有前途的候选者。
Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid–vitamin E succinate polymer (CKAAKN–HA–VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN–HA–VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN–HA–VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN–HA–VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA–VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement.
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