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靶向胰腺癌细胞的肽功能化聚合物磁性纳米颗粒。

Targeting Pancreatic Cancer Cells with Peptide-Functionalized Polymeric Magnetic Nanoparticles.

机构信息

Zhejiang University School of Medicine, Hangzhou 310009, China.

College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.

出版信息

Int J Mol Sci. 2019 Jun 19;20(12):2988. doi: 10.3390/ijms20122988.

Abstract

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.

摘要

胰腺癌是一种隐匿性和高度恶性的肿瘤,其早期诊断在癌症治疗过程中起着越来越重要的作用。在本研究中,我们开发了一种用于磁共振成像(MRI)造影剂的聚合物磁共振成像纳米平台。为了提高 MRI 造影剂的肿瘤靶向递送,我们采用了一种胰腺癌靶向 CKAAKN 肽,制备了一种肽功能化的两亲性透明质酸-维生素 E 琥珀酸聚合物(CKAAKN-HA-VES),用于递送超小超顺磁性氧化铁(USPIO),即 CKAAKN-HA-VES@USPIO。通过 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 CKAAKN 阴性的 HPDE6-C7 细胞和非靶向 HA-VES@USPIO 纳米颗粒相比,CKAAKN-HA-VES@USPIO 纳米颗粒在 CKAAKN 阳性的 BxPC-3 细胞中表现出更特异性的积聚,并且信号强度明显降低。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 阳性的胰腺癌细胞中,为胰腺癌的诊断提供了一种具有高特异性的新型聚合物 MRI 造影剂,使其成为磁共振成像增强的很有前途的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8bf/6627612/b8ccd304682e/ijms-20-02988-g001.jpg

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