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载蒽醌-聚乙二醇化 FeO 纳米粒子用于胰腺癌的 FI/MRI 双模式成像与治疗。

Emodin-Conjugated PEGylation of FeO Nanoparticles for FI/MRI Dual-Modal Imaging and Therapy in Pancreatic Cancer.

机构信息

Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210029, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Nov 6;16:7463-7478. doi: 10.2147/IJN.S335588. eCollection 2021.

Abstract

BACKGROUND

Pancreatic cancer (PC) remains a difficult tumor to diagnose and treat. It is often diagnosed as advanced by reason of the anatomical structure of the deep retroperitoneal layer of the pancreas, lack of typical symptoms and effective screening methods to detect this malignancy, resulting in a low survival rate. Emodin (EMO) is an economical natural product with effective treatment and few side effects of cancer treatment. Magnetic nanoparticles (MNPs) can achieve multiplexed imaging and targeted therapy by loading a wide range of functional materials such as fluorescent dyes and therapeutic agents.

PURPOSE

The purpose of this study was to design and evaluate a multifunctional theranostic nanoplatform for PC diagnosis and treatment.

METHODS

In this study, we successfully developed EMO-loaded, Cy7-functionalized, PEG-coated FeO (FeO-PEG-Cy7-EMO). Characteristics including morphology, hydrodynamic size, zeta potentials, stability, and magnetic properties of FeO-PEG-Cy7-EMO were evaluated. Fluorescence imaging (FI)/magnetic resonance imaging (MRI) and therapeutic treatment were examined in vitro and in vivo.

RESULTS

FeO-PEG-Cy7-EMO nanoparticles had a core size of 9.9 ± 1.2 nm, which showed long-time stability and FI/MRI properties. Bio-transmission electron microscopy (bio-TEM) results showed that FeO-PEG-Cy7-EMO nanoparticles were endocytosed into BxPC-3 cells, while few were observed in hTERT-HPNE cells. Prussian blue staining also confirmed that BxPC-3 cells have a stronger phagocytic ability as compared to hTERT-HPNE cells. Additionally, FeO-PEG-Cy7-EMO had a stronger inhibition effect on BxPC-3 cells than FeO-PEG and EMO. The hemolysis experiment proved that FeO-PEG-Cy7-EMO can be used in vivo experiments. In vivo analysis demonstrated that FeO-PEG-Cy7-EMO enabled FI/MRI dual-modal imaging and targeted therapy in pancreatic tumor xenografted mice.

CONCLUSION

FeO-PEG-Cy7-EMO may serve as a potential theranostic nanoplatform for PC.

摘要

背景

胰腺癌(PC)仍然是一种难以诊断和治疗的肿瘤。由于胰腺深腹膜后层的解剖结构,缺乏典型的症状和有效的筛查方法来检测这种恶性肿瘤,因此通常被诊断为晚期,导致生存率低。大黄素(EMO)是一种具有经济价值的天然产物,对癌症治疗具有有效治疗作用且副作用少。磁性纳米颗粒(MNPs)可以通过装载荧光染料和治疗剂等广泛的功能材料来实现多重成像和靶向治疗。

目的

本研究旨在设计和评估用于 PC 诊断和治疗的多功能治疗纳米平台。

方法

在本研究中,我们成功开发了载有 EMO、Cy7 功能化、PEG 涂层的 FeO(FeO-PEG-Cy7-EMO)。评估了 FeO-PEG-Cy7-EMO 的形态、流体动力学大小、Zeta 电位、稳定性和磁性特性。在体外和体内检查了荧光成像(FI)/磁共振成像(MRI)和治疗治疗效果。

结果

FeO-PEG-Cy7-EMO 纳米颗粒的核心尺寸为 9.9 ± 1.2nm,具有长时间的稳定性和 FI/MRI 特性。生物透射电子显微镜(bio-TEM)结果表明,FeO-PEG-Cy7-EMO 纳米颗粒被内吞到 BxPC-3 细胞中,而在 hTERT-HPNE 细胞中则很少观察到。普鲁士蓝染色也证实 BxPC-3 细胞比 hTERT-HPNE 细胞具有更强的吞噬能力。此外,与 FeO-PEG 和 EMO 相比,FeO-PEG-Cy7-EMO 对 BxPC-3 细胞具有更强的抑制作用。溶血实验证明 FeO-PEG-Cy7-EMO 可用于体内实验。体内分析表明,FeO-PEG-Cy7-EMO 能够在胰腺肿瘤异种移植小鼠中实现 FI/MRI 双模式成像和靶向治疗。

结论

FeO-PEG-Cy7-EMO 可能成为 PC 的潜在治疗纳米平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82e9/8579871/705d897dc47e/IJN-16-7463-g0001.jpg

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