Fibrin-targeting peptide CREKA-conjugated multi-walled carbon nanotubes for self-amplified photothermal therapy of tumor

Fibrin-targeting peptide CREKA-conjugated multi-walled carbon nanotubes for self-amplified photothermal therapy of tumor
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纤维蛋白靶向肽 CREKA 缀合多壁碳纳米管用于肿瘤自放大光热治疗

DOI:
10.1016/j.biomaterials.2015.11.061
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发表时间:
2016
期刊:
影响因子:
14
通讯作者:
Xinguo Jiang
Xinguo Jiang
中科院分区:
工程技术1区
文献类型:
--
作者:
Bo Zhang;Huafang Wang;Shun Shen;Xiaojian She;Wei Shi;Jun Chen;Qizhi Zhang;Yu Hu;Zhiqing Pang;Xinguo Jiang

文献摘要

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纳米药物不能有效地归巢到肿瘤部位仍然对肿瘤药物递送构成巨大挑战。以具有良好光热效应的多壁碳纳米管(MWNTs)为载体,聚乙二醇(PEG)为保护层,对纤维蛋白具有特殊亲和性的CREKA肽为靶向部分,近红外(NIR)光为外动力,设计了一种用于肿瘤光热治疗的自放大释药系统(CMWNTs-PEG)。仔细表征了自扩增靶向性质。体内温度监测实验表明,CMWNTs-PEG可以显着提高肿瘤区域的温度比其对应物后24小时的初始近红外照射。体内显像和生物分布实验表明,光照条件下IR 783标记的CMWNTs-PEG在肿瘤组织中的蓄积量是对照组的6.4倍,明显高于其他处理组;体内分布实验表明Cy 3标记的CMWNTs-PEG可存款于肿瘤血管壁、血管内和血管外间隙,其范围远大于其在肿瘤切片中的分布。药效学实验表明,4次照射后,CMWNTs-PEG几乎完全照射肿瘤异种移植物。综上所述,自扩增靶向系统CMWNTs-PEG显示出较强的肿瘤靶向能力和较强的光热治疗效果。
Inability of nanomedicine to efficiently home to tumor site still poses great challenge in tumor drug delivery. Inspired by the amplified formation of fibrin in clotting cascade, a self-amplified drug delivery system was developed for tumor photothermal therapy (CMWNTs-PEG) using multi-walled carbon nanotubes (MWNTs) with favorable photothermal effect as the vector, polyethylene glycol as the shelter, CREKA peptide with special affinity for fibrin as the targeting moiety and NIR illumination as the external power. The self-amplified targeting property was carefully characterized. Thein vivotemperature monitoring experiment demonstrated that CMWNTs-PEG could significantly elevate the temperature in the tumor region than its counterpart 24 h post an initial NIR illumination. Thein vivoimaging and biodistribution experiment showed IR783-labeled CMWNTs-PEG with illumination could accumulate in tumors tissues about 6.4-fold higher than control group, much stronger than other treatment groups.In vivodistribution experiments revealed Cy3-labeled CMWNTs-PEG could deposit on the wall of tumor vessels, intravascular and extravascular spaces, far more extensive than its counterpart in tumor slices. The pharmacodynamics experiment revealed that after four times of illumination, the CMWNTs-PEG almost totally eradiated the tumor xenografts. Altogether, the self-amplified targeting system CMWNTs-PEG showed strong tumor targeting capacity and powerful photothermal therapeutic efficacy.