PEG-functionalized iron oxide nanoclusters loaded with chlorin e6 for targeted, NIR light induced, photodynamic therapy

PEG-functionalized iron oxide nanoclusters loaded with chlorin e6 for targeted, NIR light induced, photodynamic therapy
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负载二氢卟酚 e6 的 PEG 功能化氧化铁纳米团簇用于靶向、近红外光诱导、光动力治疗

DOI:
10.1016/j.biomaterials.2013.08.041
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发表时间:
2013-12-01
期刊:
影响因子:
14
通讯作者:
Liu, Zhuang
Liu, Zhuang
中科院分区:
工程技术1区
文献类型:
--
作者:
Li, Zhiwei;Wang, Chao;Liu, Zhuang

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利用磁场将治疗诊断剂特异性递送到靶向肿瘤区域的磁靶向可以极大地提高癌症治疗效率。在此,我们负载二氢卟酚e6(Ce 6),一个广泛使用的PS分子在PDT,聚乙二醇(PEG)功能化的氧化铁纳米团簇(IONC),获得IONC-PEG-Ce 6作为治疗诊断剂的双模成像引导和磁靶向增强在体内PDT。有趣的是,在负载到PEG化的离子纳米材料上后,Ce 6的吸收/激发峰显示出明显的红移,从近似650 nm到近似700 nm,其位于具有改善的组织穿透性的NIR区域。在没有明显的暗毒性的情况下,与游离Ce 6相比,负载Ce 6的IONC PEG(IONC-PEG-Ce 6)表现出显著加速的细胞摄取,因此在低功率光暴露下提供了大大改善的体外光动力学癌细胞杀伤效率。在使用IONC PEG Ce 6证明磁场(MF)增强PDT后,我们在动物实验中进一步测试了这一概念。由于IONC的强磁性和由凝聚的PEG涂层提供的长血液循环时间,IONC PEG Ce 6显示出强的MF诱导的肿瘤归巢能力,如通过体内双模光学和磁共振(MR)成像所证明的。最后进行了基于使用IONC PEG Ce 6的磁性肿瘤靶向的体内PDT实验,在仅单次注射和MF增强的光动力治疗后,实现了高治疗功效,显著延迟了肿瘤生长。考虑到氧化铁的生物可降解性和无毒性,我们在这项工作中提出的IONC PEG Ce 6可能是一个有用的多功能药物在磁靶向下的光动力学癌症治疗的前景。(C)2013爱思唯尔有限公司版权所有。
Magnetic targeting that utilizes a magnetic field to specifically delivery theranostic agents to targeted tumor regions can greatly improve the cancer treatment efficiency. Herein, we load chlorin e6 (Ce6), a widely used PS molecule in PDT, on polyethylene glycol (PEG) functionalized iron oxide nanoclusters (IONCs), obtaining IONC-PEG-Ce6 as a theranostic agent for dual-mode imaging guided and magnetic-targeting enhanced in vivo PDT. Interestingly, after being loaded on PEGylated IONCs, the absorbance/excitation peak of Ce6 shows an obvious red-shift from similar to 650 nm to similar to 700 nm, which locates in the NIR region with improved tissue penetration. Without noticeable dark toxicity, Ce6 loaded IONC PEG (IONC -PEG-Ce6) exhibits significantly accelerated cellular uptake compared with free Ce6, and thus offers greatly improved in vitro photodynamic cancer cell killing efficiency under a low-power light exposure. After demonstrating the magnetic field (MF) enhanced PDT using IONC PEG Ce6, we then further test this concept in animal experiments. Owing to the strong magnetism of IONCs and the long blood-circulation time offered by the condensed PEG coating, IONC PEG Ce6 shows strong MF-induced tumor homing ability, as evidenced by in vivo dual modal optical and magnetic resonance (MR) imaging. In vivo PDT experiment based magnetic tumor targeting using IONC PEG Ce6 is finally carried out, achieving high therapeutic efficacy with dramatically delayed tumor growth after just a single injection and the MF-enhanced photodynamic treatment. Considering the biodegradability and non-toxicity of iron oxide, our IONC PEG Ce6 presented in this work may be a useful multifunctional agent promising in photodynamic cancer treatment under magnetic targeting. (C) 2013 Elsevier Ltd. All rights reserved.